Nitration of phenol in 1,4-dioxane

Article abstract of DOI:10.1134/S10704272150110075

The nitration of phenol with excess nitric acid in aqueous dioxane, in contrast to the nitration in aqueous ethanol, yields exclusively 2,4-dintrophenol, whereas at equimolar ratio of phenol and nitric acid the major reaction products are mononitrophenols (99%), among which the p-isomer prevails.

Full text of DOI:10.1134/S10704272150110075

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2015, Vol. 88, No. 11, pp. 1783−1787. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © Yu.G. Khabarov, D.E. Lakhmanov, D.S. Kosyakov, N.V. Ul’yanovskii, V.A. Veshnyakov, O.A. Nekrasova, 2015, published in Zhurnal
Prikladnoi Khimii, 2015, Vol. 88, No. 11, pp. 1568−1572.
ORGANIC SYNTHESIS AND INDUSTRIAL
ORGANIC CHEMISTRY
Nitration of Phenol in 1,4-Dioxane
Yu. G. Khabarov, D. E. Lakhmanov, D. S. Kosyakov, N. V. Ul’yanovskii,
V. A. Veshnyakov, and O. A. Nekrasova
Lomonosov Northern (Arctic) Federal University, nab. Severnoi Dviny 17, Arkhangel’sk, 163002 Russia
e-mail: khabarov.yu@mail.ru
Received December 9, 2014
Abstract—The nitration of phenol with excess nitric acid in aqueous dioxane, in contrast to the nitration in aque-
ous ethanol, yields exclusively 2,4-dintrophenol, whereas at equimolar ratio of phenol and nitric acid the major
reaction products are mononitrophenols (99%), among which the p-isomer prevails.
DOI: 10.1134/S10704272150110075
2,4-Dinitrophenol (DNP) is an important product of
organicsynthesis,asyntheticprecursorofvariousorganic
compounds, including sulfurous dyes [1], herbicides,
pesticides, and fungicides [2]. DNP inhibits the metal
corrosion [3] and styrene polymerization [4]; antiseptic
properties of DNP are used in preparing formulations
for wood impregnation [5]; DNP stimulates the plant
growth, influences the oxidative phosphorylation in
cells [6], and exhibits catalytic properties [7].
EXPERIMENTAL
The following chemicals were used in the study:
freshly distilled phenol (boiling point 182°С), 63% nitric
acid (chemically pure grade), 1,4-dioxane (chemically
pure grade), and ethanol (rectified, 96%).
To perform the phenol nitration, a 50-mL glass flask
equipped with a reflux condenser was charged with 1 g
of phenol and with the required volume of the reagent,
which was prepared by mixing the required volume of
concentrated nitric acid with 20 mL of 1,4-dioxane or
ethanol. The volumes of nitric acid were 0.8, 1.2, and
5 mL, which corresponds to the phenol : nitric acid
molar ratio of 1 : 1, 1 : 1.5, and 1 : 6.2, respectively.
Numerous nitration procedures have been developed
for the DNP synthesis: nitration with the classical
nitrating mixture, with liquid N2О4, oxidative nitration
of benzene with nitric acid or with air in the presence
of mercury(II) hydroxide and a small amount of nitrite.
Nitrosophenol and 2,4-dinitrochlorobenzene can also
be used as starting compounds for preparing DNP.
A procedure using sodium nitrite, oxalic acid, and
wet silicon dioxide has been developed for preparing
mono- and dinitrophenol; the reaction is performed in
methylene chloride [8]. From nitropropanedial hydrate
and 1-nitro-2-propanol, DNP is synthesized in alkaline
medium at room temperature within 18 h [9].
To determine the reaction mixture composition,
2-mL samples of the liquid were taken 10, 20, 30, and
60 min after the start of the reaction. The samples were
quickly cooled in an ice bath, after which 10 mL of
water and 2 mL of chloroform were added. The resulting
mixture was thoroughly shaken, and the lower layer was
taken after the phase separation. The extract was filtered
through a membrane filter with the pore diameter of
0.2 μm and was injected into a chromatographic column
without further pretreatment.
1,4-Dioxane is a specific and versatile solvent widely
used in chemistry and biochemistry [10–18]. It was
interesting to study the nitration of phenol with nitric
acid in 1,4-dioxane.
Analysis by chromatography–mass spectrometry
was performed with an LCMS-8030 HPLC/MS–MS
system (Shimadzu, Japan) equipped with two LC-30
1783

1784
KHABAROV et al.
pump, a DGU-5A degasser, an SIL-30 autosampler, an
STO-20A column thermostat, an SPD-M20A diode-
array spectrophotometric detector, and a tandem mass-
spectrometric detector. Chromatographic separation
was performed by reversed-phase HPLC on a TitanC18
column, 100 × 2.1 mm, 1.9 μm (Supelco, the United
States). A 40% solution of acetonitrile in 0.5% aqueous
formic acid was used as mobile phase. The flow rate
was 0.4 mL min–1. The injected sample volume was
1 μL. The electronic absorption spectra were recorded
continuously in the range 200–500 nm. The mass
spectra were recorded in the electrospray ionization
mode with the capillary voltage of 4.5 kV. The following
compounds were used as references for identification of
the reaction mixture components: phenol, p-nitrophenol,
o-nitrophenol, 2,4-dinitrophenol, and picric acid.
RESULTS AND DISCUSSION
Synthesis of 2,4-dinitrophenol from phenol is a step-
wise process. In accordance with the orienting effect of
substituents, it can be presented by the following scheme:
OH
2,4-DNP
Picric acid
However, in all the experiments performed, neither
2,6-dinitrophenol nor picric acid were detected.
The mononitrophenols formed in the first step
undergo further nitration with excess nitric acid to
form 2,4-dinitrophenol. In the second nitration step,
o-nitrophenol might transform not only into 2,4-, but
also into 2,6-dinitrophenol. At a large excess of nitric
acid, the formation of picric acid might be possible.
The phenol nitration was performed at three
temperatures: 60, 70, and 80°С. Chromatographic
analysis showed that the nitration product consisted
of 2,4-DNP and о- and p-nitrophenols (о-NP, p-NP),
with 2,4-DNP prevailing; the retention times of these
compounds are 4.73, 5.54, and 3.42 min, respectively.
In the mass spectrum, m/z for the most intense ions
[M – H]– is 183.138 Da. In addition, the results are
confirmed by data of electronic spectroscopy (the
absorption in the UV and visible ranges corresponds to
the spectra of the pure samples and to the spectra from
the NIST electronic database, http://webbook.nist.gov/
chemistry/). The absorption maxima were observed at
the following wavelengths (nm); for phenol, 271; for
о-nitrophenol, 276 and 351; for p-nitrophenol, 316; for
2,4-dinitrophenol, 258; and for p-nitrosophenol, 245.
τ, min
The examples of the chromatograms are shown in
Figs. 1 and 2. Peak 1 (Fig. 2) was identified on the basis
of the mass spectrum as the peak of p-nitrosophenol.
In the MS1 spectrum, there is an ion with m/z 122 Da,
corresponding to the [M – H]– ion. In the MS2 spectrum
of the deprotonated molecule, obtained at the collision
Fig. 1. Chromatogram of the products of phenol nitration
with nitric acid in aqueous alcohol. Reaction time 30 min,
molar ratio of nitric acid and phenol 6.2; the same for Fig. 2.
(D) Optical density and (τ) time; the same for Fig. 2. (1) p-NP,
(2) DNP, and (3) o-NP.
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 88 No. 11 2015

NITRATION OF PHENOL IN 1,4-DIOXANE
1785
energy of 25 eV, there is the only fragment ion with
m/z 92 Da, formed by elimination of the nitroso group
from the parent ion (Δm/z = 30 Da). The presence of
small amounts of p-nitrosophenol suggests that the
phenol nitration can involve not only electrophilic
nitration, but also nitrosation with the initial formation
of p-nitrosophenol, which is subsequently oxidized to
p-nitrophenol.
Nitration of phenol with nitric acid in aqueous
ethanol. To obtain comparable results, the nitration of
phenol with nitric acid in the presence of ethanol was
performed at 80°С. The results of determining the
reaction mixture composition from the ratios of the
areas of the chromatographic peaks at a wavelength of
280 nm for phenol nitration with nitric acid (Table 1)
shows that phenol is completely consumed in the first
10 min of the reaction, and the main reaction products
are o- and p-nitrophenols, and also 2,4-dinitrophenol.
The total content of these derivatives in the reaction
products was more than 99.5%. The ratio of the o- and
p-isomers after the 10-min reaction was close to 2 : 1,
which corresponds to the ratio of the amounts of the sites
accessible to nitration in the o- and p-positions of the
phenol molecule. Then, the ratio of the mononitrophenol
isomers changes with time. o-Nitrophenol is consumed
faster, and its content in the reaction products decreases
from 57.4 to 22%, whereas the content of p-nitrophenol
decreases from 29.1 to 24.4%.
τ, min
Fig. 2. Chromatogram of the products of phenol nitration
with nitric acid in aqueous dioxane. (1) p-Nitrosophenol,
(2) phenol, (3) p-NP, (4) DNP, and (5) o-NP.
obtained with ethanol, is close to 1 : 2 instead of the
expected 2 : 1. This may be due to strong solvating
action of dioxane molecules. Solvation occurs with the
participation of phenol hydroxy groups. The solvates
shield the o-positions in the phenol molecule. As the
nitric acid amount was increased to 1.5 mol per mole of
phenol, the content of 2,4-DNP regularly increased (to
19%). The content of p-nitrophenol did not noticeably
change with time, whereas o-nitrophenol was consumed.
In both cases, phenol was consumed in the first 10 min
of the reaction.
Thus, in phenol nitration in aqueous dioxane at
equimolar ratio of nitric acid and phenol, the major
reaction products are mononitrophenols, among which
p-nitrophenol prevailed. With excess nitric acid,
2,4-dinitrophenol is formed exclusively. Nitration of
phenol in aqueous dioxane occurs considerably faster
than in aqueous ethanol.
Nitration of phenol with nitric acid in aqueous
dioxane. The phenol nitration in aqueous dioxane
appeared to be very efficient and considerably faster
than in aqueous ethanol. Up to five different reaction
products were detected by HPLC. With dioxane as
solvent, similarly to the reaction in ethanol, phenol is
completely consumed within 10 min, but the content
of 2,4-dinitrophenol in the reaction products is as high
as 87.5%, whereas the content of mononitrophenols
does not exceed 10%. In the subsequent process,
p-nitrophenol fully disappears, and the content of the
o-nitrophenol impurity decreases from 8.3 to 0.8%.
Table 1. Variation of the reaction mixture composition with
time in the course of phenol nitration with nitric acid in
aqueous ethanol
Component content in reaction products, %
τ,
min
The influence of the ratio of nitric acid and phenol
in nitration in aqueous dioxane is shown in Table 2.
With equimolar amounts of nitric acid and phenol,
the major products are mononitrophenols, with less
than 1% content of 2,4-dinitrophenol. As expected, o-
and p-nitrophenols are the major products, but their
ratio in the reaction mixture, in contrast to the results
p-NP
DNP
o-NP
10
20
30
60
28.1
29.1
25.5
24.4
14.1
25.2
32.5
53.4
57.4
45.6
41.9
22.0
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 88 No. 11 2015

1786
KHABAROV et al.
Table 2. Composition of the products of phenol nitration with nitric acid in aqueous dioxane in relation to the reactant ratio
Reaction conditions
Content in reaction products, %
Т, °С
HNO3/phenol molar ratio
τ, min
p-NP
DNP
o-NP
80
80
80
80
80
80
80
80
60
60
60
60
70
70
70
70
80
80
80
80
1
10
20
30
60
10
20
30
60
10
20
30
60
10
20
30
60
10
20
30
60
59.0
58.2
46.6
49.7
52.3
62.4
55.2
50.7
44.3
39.7
34.4
29.0
33.6
24.8
17.6
8.9
0.6
0.4
34.7
36.7
50.1
47.3
39.2
28.2
31.8
29.2
36.7
27.7
21.7
11.3
18.1
9.0
1
1
0.3
1
0.4
1.5
1.5
1.5
1.5
6.2
6.2
6.2
6.2
6.2
6.2
6.2
6.2
6.2
6.2
6.2
6.2
7.7
8.7
12.4
19.6
18.0
31.3
42.6
58.2
47.0
64.7
76.1
87.5
87.5
92.4
95.5
96.1
4.4
1.4
8.3
3.2
5.4
0.5
2.6
–
0.8
–
CONCLUSIONS
REFERENCES
1. Zollinger, H., Color Chemistry. Synthesis, Properties and
Applications of Organic Dyes and Pigments, Weinheim:
Wiley, 2003.
The use of dioxane as solvent in phenol nitration
allows directional synthesis of 2,4-dinitrophenol and
can favor the development of a highly efficient process
for 2,4-dinitrophenol production.
2. RF Patent 2435369, Publ. 2011.
3. RF Patent 2299270, Publ. 2006.
4. RF Patent 2391328, Publ. 2010.
ACKNOWLEDGMENTS
5. Richardson, B.A., Wood Preservation, New York: Spon,
The study was financially supported by the Ministry
of Education and Science of the Russian Federation
(project no. 1321) using the equipment of the Arktika
Center for Shared Use of Scientific Equipment [Northern
(Arctic) Federal University] (unique work identifier
RFMEFI59414X0004).
1993.
6. Tewari, A., Ali, T., Ali, A., et al., Brit. J. Anaesth., 2009,
vol. 102, no. 4, pp. 566–567.
7. Da, C.-S., Che, L.-P., Guo, Q.-P., et al., J. Org. Chem.,
2009, vol. 74, no. 6, pp. 2541–2546.
8. Zolfigol, M.A., Ghaemi, E., and Madrakian, E., Synth.
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 88 No. 11 2015

NITRATION OF PHENOL IN 1,4-DIOXANE
1787
Commun., 2000, vol. 30, no. 10, pp. 1689–1694.
14. Sharma, N., Kaistha, A., Bhatt, S.S., and Chaudhry, S.C.,
Synth. React. Inorg. Met.-Org. NanoMet. Chem., 2003,
vol. 33, no. 3, pp. 497–507.
9. US Patent 6960696, Publ. 2005.
10. Kochetova, L.B., Kalinina, N.V., Kuritsyn, L.V., and
Kustowa, T.P., Russ. J. Gen. Chem., 2015, vol. 85, no. 6,
pp. 1416–1423.
15. Yang, Z.-W., Liu, Y.-C., Liu, D.-C., et al., J. Hazard.
Mater., 2010, vol. 177, pp. 938–943.
16. Zakaria, N.D., Yusof, N.A., Haron, J., andAbdullah,A.H.,
11. Ryseck,G.,Villnow,T.,Hugenbruch,S.,etal.,Photochem.
Photobiol. Sci., 2013, vol. 12, pp. 1423–1430.
Int. J. Mol. Sci., 2009, vol. 10, pp. 354–365.
17. Amigues, E.J. and Migaud, M.E., Tetrahedron Lett.,
12. Moss, R.A., Wang, L., Odorisio, C.M., et al., J. Phys.
Chem. A, 2010, vol. 114, no. 1, pp. 209–217.
2004, vol. 45, pp. 1001–1004.
18. Barannikov, V.P. and Guseinov, S.S., Russ. J. Phys.
Chem. A, 2014, vol. 88, no. 2, pp. 254–258.
13. Ruidiaz, M.A., Delgado, D.R., Martinez, F., and Mar-
cusb, Y., Fluid Phase Equil., 2010, vol. 299, pp. 259–265.
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 88 No. 11 2015