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, electrophilic 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
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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 studentfriendly, 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 regioselectivity 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.
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.
Published: November 30, 2011 268
dx.doi.org/10.1021/ed100957v | J. Chem. Educ. 2012, 89, 268−270
Journal of Chemical Education
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Scheme 2. Mechanism of Para Nitration of Phenol
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-nitrophenols, 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.
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.
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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
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 temperature. 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.
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.
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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 269
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Laboratory Experiment
(3) (a) Bacharch, G. J. Am. Chem. Soc. 1927, 40, 1522. (b) Peng, X.; Suzuki, H.; Lu, C. Tetrahedron Lett. 2001, 42, 4357−4359. (c) Strazzolini, P.; Giumanini, A. G.; Runcio, A. Tetrahedron Lett. 2001, 42, 1387−1389. (d) Ramana, M. M. V.; Malix, S. S.; Parihar, J. A. Tetrahedron Lett. 2004, 45, 8681−8683. (e) Hua, R.; Yin, Y. J. Org. Chem. 2005, 70 (22), 9071−9073. (f) Koley, D.; Col n, O. C.; Savinov, S. N. Org. Lett. 2009, 11 (18), 4172−4175. (4) (a) Nagy, S.; Zubkov, E.; Shubin, V.; Paukshtis, E.; Razdobarova, N. Acta Chim. Hung. 1992, 129, 576. (b) Nagy, S.; Shubin, V.; Vostrikova, L.; Ione, K. J. Mol. Catal. 1991, 64, 31. (c) Outertani, M.; Giraro, P.; Kagan, H. Tetrahedron Lett. 1982, 23, 4215. (d) Samjadar, S.; Becker, B.; Banik, B. Tetrahedron Lett. 2000, 41, 8017. (e) Zolfigol, M.; Madrakian, E.; Ghaemi, E. Molecules 2001, 6, 614. (f) Zolfigol, M.; Madrakian, E.; Ghaemi, E. Molecules 2002, 7, 734. (g) Zolfigol, M.; Madrakian, E.; Ghaemi, E. Synth. Commun. 2000, 30, 1689. (h) Gigantee, B.; Prazeres, A.; Maarcelo, M.; Laszlo, P. J. Org. Chem. 1995, 60, 3445. (i) Rajagopal, R.; Srininasan, K. Synth. Commun. 2003, 33, 961. (5) (a) Bose, A.; Ganguly, S.; Manhas, M.; Rao, S.; Speck, J. Tetrahedron Lett. 2006, 47, 1885. (b) Selvam, J.; Suresh, V.; Rajesh, K.; Reddy, S. Tetrahedron Lett. 2006, 47, 2507. (c) Anuradha, V.; Srinivas, P.; Aparna, P.; Rao, J. Tetrahedron Lett. 2006, 47, 4933. (6) Esteves, P. M.; Carneiro, J. W. M.; Cardoso, S. P.; Barbosa, A. G. H.; Laali, K. K.; Rasul, G.; Surya Prakash, G. K.; Olah, G. A. J. Am. Chem. Soc. 2003, 125 (16), 4836−4849. (7) Microwave-Enhanced ChemistryFundamentals, Sample Preparation, and Applications; Kingston, H. M., Haswell, S. J., Eds.; American Chemical Society: Washington, DC, 1997. (8) Carlson, S. S.; Stewart, J.; Technique in Organic Chemistry, 2nd ed.; Weissberger., A., Ed.; Wiley-Interscience: New York, 1965; Vol. 4, p 49.
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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CONCLUSION 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.
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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.
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AUTHOR INFORMATION
Corresponding Author
*E-mail::
[email protected].
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ACKNOWLEDGMENTS Authors thanks to UGC-DAE CSR (CRS K-04-19), Indore, India, for their financial support. H. Mande thank the UGCDAE, CSR for the fellowship.
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REFERENCES
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