Nitration of Phenols A Two-Phase System Petrus J. Zeegers School of Physical Sciences, Flinders University, SA 5042, Australia Eledronhilic aromatic substitution reactions are universal to mist undergraduate organic chemistry laboratory courses. Nitration is often selected a s the reaction of choice to illustrate the nature of these reactions and the effect of substituents in directing the incoming electrophile. The nitration of phenols is, however, often overlooked because of the inherent difficultv associated with these activated molecules, not the least of which is the messiness involved. In a recent article in this .Journal McCullough ( 1 1 described a method for the nitration of phenol that involved the elimination of the water oresent in the 70ri nitric acid used. The method was usedio prepare 2,4-dinitrophenol. The method described below is for the facile and clean mononitration of phenols with only trace amounts of polynitrated products. I n 1912 Robertson and Briscoe (2)first reported the nitration of thymol by diluting the nitric acid with diethyl ether. In our recent research (3) we have used a modification of this system and that proposed by Overtani, Girard, and Kagan ( 4 ) to develop a two-phase nitration system that can be used successfully to nitrate phenols with excellent yields in the hands of inexperienced undergraduate students. The addition of a catalytic amount of NaNOz leads to a marked uccrleration of ;he reaction rate. with: out the addition of the catalyst the nitration still proceeds but a t a much reduced rate (3).A variety of organic solvents have been used successfully for the two-phase nitration procedure of which dietbyl ether and dichloromethane were the most effective. At an acid concentration of 3M H.SO& no hvdrolvsis " . of the diethvl ether was evident. One other product formed during the course of the reaction is 1.4-benzoauinonerP8'i, formed bv the oxidation of'phenol b i nitric kid. This product also is easily identifiable by GLC TLC, or 'H-NMR and is isolable. As well as the teaching of aspects of aromatic substitution reactions we also have introduced the use of chromatography for product identification and purification. The course of the reaction can be monitored readily by TLC, GLC, or 'H-NMR by the removal of a small sample of the top ether layer. For those laboratories with access to desktop Molecular Orbital packages, product isomer ratios can be calculated by reference to charge densities or electron distributions.
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Materials and Methods All materials mentioned are available commercially available. The chemicals were AR grade and were used without further purification. TLC used Merck Kieselgel 60F254 plate and the spots identifiedpder a 254 nm lamp. 'H-NMR were recorded on a Varian EM 360 in deuterochloroform with TMS as internal standard. GLC was performed on a Perkin-Elmer Sigma 3B with flame ionization detector and electronic integrator. A 3% QF-1 stainless steel column was used. Phenol (5.0 g, 0.053 mol) in diethyl ether (50 mL) was added to NaNQ3 (5.0 g, 0.059 mol) in 3M HzS04(50 mL) containing a trace amount of NaN02 (0.05 g) and the resultant two-phase mixture stirred mechanically a t room tem1036
Journal of Chemical Education
perature (20-25 OC) and monitored every 30 min till no further starting material was detectable (4-6 h) by GLC or TLC. Completion of the reaction usually occurred during the course of a single day laboratory session. The work-up procedure could be done on the following day. The organic phase was isolated and solvent removal yielded an or&e/hrown solid. This is added to watcr and subsequently steam distilled to isolate the o.nitrophenol, thep-nitn~pheno1 isomer is then crystallized from the aqueous residue. Altcrnativelv o-nitrophenol could be isolated bv extraction of the total product with hexane (3 x 50 m~).-solventremoval and recrystallization from aqueous ethanol afforded yields of the bright yellow product (mp = 44 'C) that was up to 43%. The p-nitrophenol (mp = 114 'C) was obtained by crystallization of the hexane insoluble portion with HCW water.. eivine a yield of the order of 25%.Athird alter" native is to chromatograph the total product. Column chromatomaohv was conducted usine Merck Kieseleel60 17% 230 mesh),"30 g per gram of prodkt and the colimn eluted with hexane:ethyl acetate (10:l). Five-milliliter fractions were collected and compared to purified reference compounds by TLC. For phenol nitration the order of product elution is o-nitrophenol, 1,4-benzoquinone, and p-nitrophenol. An illuminating alternative to phenol is the use of m-cresol as substrate. -me addition, &the three position, of the methyl m u p that is also activating and orthopara directing, means that there are now threeunequal s i t k of attack by the electrophile. The reaction time also is reduced to 10-15 min normally. Again the course of the reaction can be monitored easily by TLC or GLC, but the rapid rate of this reaction makes it a less viable exercise than is the case for phenol. 'H-NMR is now also a method of product identification as the chemical shift for the ArMe peaks for the nitrated products and starting material are suficiently separated. Quantification of the product ratio is, however, less certain due to the proximity of the ArMe peaks for the 2-nitro and 4-nitro isomers that tend to overlap. Separa-
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Product ldentificatibn upon the Nitration of mCresol, 10 min at 25 O C Compound
GLC % Product ArMe time, min. by GLC 6. ppm
rncresol
3.60
0
290
1.4deep yellow solid benzoquinone mp = 112 'C
5.80
7.5
2.05(d)
2-nitro
bright yellow solid mp = 39 'C
7.85
22.2
2.60
6-nitro
yellow solid mp=54'C
8.95
28.5
2.40
4-nitro
tan solid mp = I28.C
12.75
41.8
2.70
GLC Conditions were as follows: 100 Ffor 5 min, ramp rate 10 O per min ' far 10 min. 200 C
tion of the nitration products is achieved best by column chromatography as described above for phenol. For nitration of m-cresol, the order of product elution is: 6-nitro-mand cresol, 2-nitro-m-cresol, 3-methyl-1,4-benzoquinone, 4-nitro-m-cresol. To illustrate the activating or deactivating tendency of other substituent groups several other three-substituted phenols also have been nitrated. 3-Hydroxyacetophenone is considered to be one of the most useful because of the deactivating nature of the ketone functionality and the ease of product identification for this wmpound.
In summary, the nitration of phenols using the twophase procedure can be used to illustrate some of the chemistry of aromatic compounds and to explore the qualitative and quantitative aspects of some chromatographic techniques and 'H-NMR. Literature 1. McCullough,T. J. C b m . Edvc 1980.61.801.
2. Robemon, P.W ;Briscoe, H. V. A. J Chem. Soe. 1918,196P1967. 3. Thompson,M.J:Zeegers, P J. lktmhdmn 1989,45(1),191-202. 4. Overtani, M.: Girsrd, P: Ksgao,H.B. Tetrakedmn Lett.1982,23(42),4315-4318.
Volume 70 Number 12 December 1993
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