Laboratory Experiment

pubs.acs.org/jchemeduc

Nitration of Phenols Using Cu(NO3)2: Green Chemistry Laboratory

Experiment
Urvashi Yadav, Hemant Mande, and Prasanna Ghalsasi*
Department of Chemistry, Faculty of Science, The M. S. University of Baroda, Vadodara 390 002, India
*
S Supporting Information

ABSTRACT: An easy-to-complete, microwave-assisted, green chemistry, electro-

philic nitration method for phenol using Cu(NO3)2 in acetic acid is discussed.
With this experiment, students clearly understand the mechanism underlying the
nitration reaction in one laboratory session.

KEYWORDS: Second-Year Undergraduate, Upper-Division Undergraduate, Laboratory Instruction, Organic Chemistry,

Hands-On Learning/Manipulatives, Chromatography, Electrophilic Substitution, Green Chemistry, Hydrogen Bonding,
NMR Spectroscopy

O ne of the messiest experiments to be found in organic

chemistry laboratories is the nitration of phenol.1 The
instantaneous result of mixing of the reactants is a black and
sticky mass that adheres to the stirring rod and flask. Most of
the methods reported for nitration2 of aromatic compounds
require a mixture of nitric and sulfuric acid (Scheme 1). Use of
Scheme 1. Traditional Nitration of Phenol
such corrosive reagents (especially in excess) creates serious
environmental issues and the treatment and disposal of the
used mixed acid is expensive. These methods also suffer from
disadvantages such as overnitration, strongly acidic medium,
tedious workup, and safety issues.
To overcome these problems, alternative procedures for the
nitration of phenol have been reported in literature.3 Some of
these methods include use of acetyl nitrate (AcONO2), triflyl
nitrate (TfONO2), NaNO3/HCl with catalytic amounts of
La(NO3)3, Bi(NO3)3/montmorillonite KSF, NaNO3/wet SiO2,
NaNO2/silica sulfuric acid, Mg(NO3)2·6H2O, Cu(NO3)2/clay,
Fe(NO3)3·9H2O/ionic liquid, and VO(NO3)3.4 Other methods
such as reaction of metal nitrate/clay combinations activated by
acetic anhydride, calcium nitrate and microwave, zirconyl
© 2011 American Chemical Society and
Division of Chemical Education, Inc.
nitrate, and p-toluenesulfonic acid/Ni(NO3)3 have also been
developed.5 A majority of these methods are used and
developed for advance research purposes. Here a student-
friendly, easy-to-complete, nitration method for phenol using
Cu(NO3)2 in acetic acid is presented.
Nitration of phenol compounds is an important chemical
process that has wide applications in dyes, pharmaceuticals,
agrochemicals, explosives, and plastic industry. Electrophilic
nitration of aromatic compounds is mediated by the nitronium
ion (NO2+) according to the current theory about the
mechanism of nitration.6 In these reactions, NO2+ interacts
with the aromatic ring to give the desired product. In case of
nitration of phenol, NO2+ ion can attack at two possible sites,
ortho or para relative to the −OH group of phenol. This makes
the reaction interesting from the mechanistic and regioselec-
tivity point of view. The mechanism for the para nitration of
phenol is shown in Scheme 2 (a similar mechanism exists for
the ortho product).
The present experiment effects nitration of phenol using an
environmentally friendly nitrating mixture with a high
regioselectivity. Copper(II) nitrate is used as a nitrating
agent. Cu(NO3)2 reacts with glacial acetic acid to give
HNO3, as shown in Scheme 3. Copper acetate, the byproduct
in this nitration reaction, is one of the main reactant in the
preparation of fungicide (Paris Green or Schweinfurt Green)
and a green pigment. It is also used as a reagent for the
synthesis of various inorganic and organic compounds.
Published: November 30, 2011
268 dx.doi.org/10.1021/ed100957v | J. Chem. Educ. 2012, 89, 268−270
Journal of Chemical Education
Scheme 2. Mechanism of Para Nitration of Phenol
Scheme 3. Green Chemical Generation of HNO3
The present regioselective nitration of phenol is simple as
well as a high-yielding reaction that is ideally suitable for an
undergraduate organic laboratory course. It can be completed
within 1 min with microwave irradiation and the students have
time to purify the product in the time allotted for the laboratory
session.
■ EXPERIMENT OVERVIEW
The overall reaction is shown in Scheme 4. Microwave heating
shortens the reaction time and improves yields thereby allowing
Scheme 4. Green Nitration of Phenol
a scale down of reagents.7 The time saved allows for additional
chemistry or more in-depth analyses of products by the
students. Aqueous workup, including extraction of the product
into ethyl acetate, followed by column chromatography or
steam distillation, gives pure samples of nitro phenols, which
are characterized by IR and 1H NMR. This method is
compatible with a green chemistry approach. The reagents
and byproducts in this reaction are safe and eco-friendly.
Selectivity in the site of nitration has been better achieved.
269
■
Laboratory Experiment
EXPERIMENTAL PROCEDURE
Using Laboratory Microwave
Phenol (1.000 g, 0.0106 mol) and 5 mL of acetic acid were
mixed in a 50 mL glass round-bottom flask and placed on a
Weflon holder P/N SGL0020 in the center of the microwave
(START SYNTH; serial no.: 131568). Cu(NO3)2 (2.385 g,
0.0127 mol) was added to the mixture slowly and the small
neck of the flask was closed with a glass stopper. Upon addition
of Cu(NO3)2, the color of the reaction mixture changed to
reddish brown and brown fumes were generated. The reaction
mixture was stirred via a magnetic stir bar and plate. The
reaction was performed with the microwave oven at a power of
320 W, heated to 120 °C via the microwave temperature
control, and held at this temperature for 1 min. Upon
completion of the reaction (i.e., after heating), the color of
the mixture darkened and additional brown fumes were
generated. The mixture was allowed to cool to room
temperature. Then, 10 mL of ethyl acetate was added and
the mixture stirred. The slurry was filtered. The solid generated
was Cu(OOCCH3)2 and the filtrate contained the nitration
product. Water, 10 mL, was added to the filtrate and ethyl
acetate layer separated from it. The ethyl acetate layer was
checked with the thin-layer chromatography (TLC) to
determine presence of impurity or byproducts. Hexane/ethyl
acetate (8:2) was used as the TLC solvent.
The students isolated the products by either steam
distillation or column chromatography. Half of the students
used one technique and the other half of the students used the
other technique. In this way, the students were exposed to both
techniques. Steam distillation8 is a means of separating and
purifying organic compounds. The operation consists of
volatilizing a substance that has a vapor pressure of at least
5−10 mm at 100 °C. This volatilization can be achieved by
passing steam into a mixture of the compound and water.
Present reaction gives two products, ortho- and para-nitro-
phenols, which due to their different hydrogen-bonding pattern
can be separated using steam distillation. Steam distillation of
reaction mixture gives almost the same yield as obtained from
column chromatography. The detailed procedures for both the
steam distillation and the column chromatography are available
in the Supporting Information.
Using Domestic Microwave
Phenol (1.000 g, 0.0106 mol) and 5 mL of acetic acid were
mixed in a 100 mL beaker. Then, Cu(NO3)2 (2.385 g, 0.0127
mol) was added to the mixture slowly. Brown fumes were
generated upon addition. Once the addition was over, the
beaker containing reaction mixture was placed in the
microwave oven (model GMG 17E 07 WHGX; serial no.:
6D0807) and covered with a Pyrex watch glass. It was heated
for 1 min with a 10 s pulse at 320 W. Once the reaction was
complete, the mixture was allowed to cool to room temper-
ature. Then, 10 mL of ethyl acetate was added and stirred well
using the stirring plate. The solid slurry was filtered; the solid
was Cu(OOCCH3)2 and the filtrate contained the expected
nitration product. Products were separated and purified using
the above method.
■ HAZARDS
Phenol is corrosive if inhaled or ingested, or if comes in contact
with the skin may cause burns. Inhalation of acetic acid and
silica gel may cause irritation of respiratory tract that is
characterized by coughing or chocking. Hexanes and ethyl
dx.doi.org/10.1021/ed100957v | J. Chem. Educ. 2012, 89, 268−270
Journal of Chemical Education Laboratory Experiment

acetate are volatile and flammable organic solvents, hence,
avoid exposing them to flames and heat sources. Copper(II)
nitrate is a strong oxidizing agent and moderately toxic by
ingestion. Students and instructors should wear goggles, gloves,
and lab coats or aprons. The TLC plate should be handled with
tweezers, not by hand.
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■
RESULTS AND DISCUSSION
The reaction showed reproducible results performed in a
microwave oven set at 320 W. Acetic acid, an excellent absorber
of microwave energy, acts as a solvent as well as reactant and
thus was able to shorten the reaction time to 1 min. One
minute of microwave heating produced overall yields in the
range from 70.0% to 80.0%, with more than 80% para isomer.
The reaction was monitored using TLC and purified using
column chromatography and steam distillation. Various molar
ratios of metal nitrate to phenol were used and the best results
were obtained with a ratio of 1:2. Melting point values were
matched with literature values, 113.5 °C for para-nitrophenol
and 45.5 °C for ortho-nitrophenol.
With the time saved in the reaction, the experiment was
completed in 2 to 3 h with purification of reaction mixture by
column chromatography and steam distillation. The remaining
time was used for a discussion of 1H NMR and IR spectra given
to the students by the instructor and to teach students literature
searching using SciFinder Scholar.
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■
(8) Carlson, S. S.; Stewart, J.; Technique in Organic Chemistry, 2nd
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CONCLUSION p 49.
An easy, quick, and inexpensive electrophilic aromatic nitration
reaction via a green chemistry method using microwaves is
described. The starting material and final product are analyzed
using melting point or boiling point, IR spectroscopy, and TLC
methods. The additional benefit associated with microwave
heating instead of the conventional methods of heating is rate
enhancement. Along with prelab and postlab analysis, present
experiment definitely helps student understand the mechanism
of nitration reaction.

■
*
ASSOCIATED CONTENT
S Supporting Information

Student procedure; instructor notes; IR and 1H NMR data of

the final product; experimental procedure; sample questions for
the students. This material is available via the Internet at
http://pubs.acs.org.

■ AUTHOR INFORMATION
Corresponding Author
*E-mail:: prasanna.ghalsasi@gmail.com.

■ ACKNOWLEDGMENTS
Authors thanks to UGC-DAE CSR (CRS K-04-19), Indore,
India, for their financial support. H. Mande thank the UGC-
DAE, CSR for the fellowship.

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270 dx.doi.org/10.1021/ed100957v | J. Chem. Educ. 2012, 89, 268−270