1. K. Dyall
Newcastle. Shortlano, ~ . s . wA.stra1.a .. Universitv , of ~~
1I
An Experiment in Activated Aromatic Nucleophilic Substitution
This article describes .an experiment which brings the advanced student into contact with some of the basic ideas of physical organic chemistry, and also illustrates the use of infrared spectroscopy for identification of reaction products. The experiment involves preparing the intermediates formed during activated aromatic nucleophilic substitution, and a study of their decomposition on treatment with mineral acid. The products obtained yield information about the relative abilities of potential anions to function as leaving groups. The most widely accepted pathway for nucleophilic displacement from an aromatic nucleus, activated by electron-withdrawing suhstituents (e.g., nitro, cyano) ortho or para to the seat of substitution, is the intermediate complex mechanism ( 1 , 2 , 3 ) . The mechanism is illustrated for a picryl derivative, Pic X, reacting with an anion, y: -.
(Pic X)
\
tion of the Meisenheimer intermediate formed from methyl picryl ether and sodium methoxide has been described by Fendler (11). Treatment of the Meisenheimer intermediate (I above) with aqueous mineral acid converts it quantitatively into either Pic X or Pic Y, or alternatively into a mixture of these two compounds. One can regard this process either as a nnimolecular dissociation (11) of the intermediate I, with trapping of the anion produced by protons (lo), or as a similar dissociation of a, molecule of the intermediate protonated on a nitro group. I n either instance, the relative proportions of Pic X and Pic Y formed will be governed by the ability of X : - and Y: - to depart from the intermediate. The following experiment permits these relative leaving group abilities to be measured. The Experiment
Methyl picryl ether and 1,3,5-trinitrobenzene are commercially available, and the preparations of ethyl and phenyl picryl ether from picryl chloride have been described in the literature (10). We provide the four picryl compounds and the methanolic sodium methoxide solutions to the students. The methanol and ethanol must he dry, reagent-grade solvents.
I
(Pic Y)
The intermediate I is a cyclohexadienide anion, with sp3 hybridization at the seat of substitution. If neither X nor B is a good leaving group, and if the substituents are sutticiently effective a t delocalizing negative charge, the intermediate is stable enough to be isolated as a cryst,alline metal salt. The isolation of such a salt, formed by treating 1,3,5-trinitrobemene with methanolic potash, was first reported by Lobry de Bruyn and van Leent (4) in 1895. Similar salts were isolated by Jackson and Boos (5) and by Meisenheimer (6) after treating 2,4,64rinitroanisole (methyl picryl ether) with metal alkoxides. These salts have come to be known as Meisenheimer complexes, after the distinguished German chemist who made extensive investigations of t.heir preparation and properties. The structures of these salts have recently been firmly established by studies of the NMR (7-9) and infrared (10) spectra. The potential energy diagram for form*
Safety Precautions. Picry1 cmpounds are potentially explosive and s t d x l s should practice due safety precautions. These compounds must not be stwed i n glass-stoppered c o n t a i w s , OT be subjected to abrasion. Steel or nickel spatulas m y strike sparks, and therefwe brass, hwn, or plastic spatulas should be used. Steam baths are to be prefwred to electrical heating mantles for distilling the ehlorqfonn from the picryl comprmnds. Students should wear safety glasses while handling these compounds. The 0.6 M sodium m e t h i d e aolutian is eovosiue, and must be washed out of apparatus joints and stopcocks as quickly as possible.
Preparation and Decomposition of the Meisenheimer Intermediates. The following preparations of Meisenheimer intermediates are required. 1. Methanolic sodium metboxide (0.5 M) added to 1,3,5-trinitrobenzene dissolved in methanol. 2. Methanolic sodium methoxide (0.1 M)added to phenyl picryl ether dissolved in methanol. 3. Ethanolic sodium ethoxide (0.1 M) added to methyl picryl ether dissolved in ethanol. The picryl compound (0.50 mmoles) is dissolved by warming in the appropriate anhydrous alcohol (usually 10 ml, but the phenyl ether requires 20 ml) in a 100-ml two-necked flask fitted with a drying tube and a dropping funnel. The solution is cooled to room temperature and then shaken during the dropwise addition (10 min) of the sodium alkoxide solution (5 ml). After Volume 43, Number 12, December 1966
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663
the mixture has been allowed to stand for a further period of 10 min, aqueous 0.1 M sulfuric acid (30 ml) is added in one portion, with shaking, and the bright red color of the Meisenheimer complex is immediately destroyed. Methyl picryl ether forms an insoluble complex with sodium ethoxide, but the precipitated crystals react quickly with the acid on shaking. The reaction mixture is extracted with three 10-rnl portions of chloroform, and the alcohol (or phenol) is largely removed from the combined extracts by shaking with water (10 ml). The chloroform solution is dried (30 min) over anhydrous sodium sulfate, and the solvent is then distilled from a steam bath. Gentle water pump suction is required to remove the last traces of solvent and any remaining alcohol or phenol. We ask students to distill from a tared flask, so that the efficiency of the isolation procedure can be checked by weighing the product. Analysis of the product will be almost meaningless if the recovery of it is not high. Spectroscopic Measurements. The infrared spectra of the reaction products in chloroform solution are recorded from 1700 to 800 cm-I. A suitable concentration for sample cells of 0.1 mm path-length is obtained by dissolving the reaction product in 10 ml of spectrograde chloroform. Unless the two cells used in a double-beam spectrophotometer are very well matched, the strongest of the chloroform bands will he recorded, but these will not interfere with the spectral comparisons required in this experiment. Picryl compounds are not sufficiently soluble to permit the spectra to he measured in a more transparent solvent. The students can readily predict the four possible products formed by decomposition of the above Meisenheimer intermediates, and can run spectra of these compounds for comparison with the spectra of the reaction products. (A suitable concentration for all four picryl compounds in chloroform soIution is 0.05 M for sample cells 0.1 mm thick.) The spectra of all four picryl compounds should be recorded at the same concentration since they will he used for a semiquantitative analysis of a two-component mixture. A pair of students can complete the experiment in two 3-hr driods. Results
Experiment (1) above yields only l,3,5-trinitrobenzene, and (2) gives only methyl picryl ether. As indicated by the figure, these compounds are readily identified by comparison of the infrared spectra. The four picryl compounds used here also display spectral differences additional to those shown for the 1175-875 em-' region. This region was chosen for illustrative purposes because it is free of solvent absorptions if the two sample cells are reasonably well matched. Experiment (3) yields a mixture of methyl picryl ether and ethyl picryl ether. These two compounds give rise to characteristic infrared hands at 982 and 1006 cm-' respectively (Fig. 1). A semiquantitative analysis, based on the intensities of these bands in the spectra of the mixture and of the two pure compounds, indicates that the proportions of these two compounds are about equal. The rnmbination of the three sets of results indicates that the leaving group ability decreases in the order PhO- > MeO-, EtO- > H-. 664
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Journal of Chemical Education
The above order of leaving group abilities from carbon can be predicted qualitatively by examining the pKa values of the conjugate acids. The available values (13, 13) for aqueous solutions a t 2 5 T , are 9.99 for phenol, -15.9 for ethanol, and 15.5 for methanol. It must be remembered, of course, that pKa is a measure of the ability of an anion to depart from hydrogen.
Infrared spectra (1175-875 cm-'1 10I"ti0".
of picryl compovnds in chloroform
The validity of the results obtained in these esperiments with Meisenheimer intermediates should be critically examined by the students. The results mould be quite worthless if treatment of the substrate Pic X with the nucleophile Y :- did not lead to high conversion to the intermediate under the experimental conditions. Not all the required equilibrium constants for forination of the intermediates are known. The available value of 15 l mole-' for 1,3,5-trinitrobenzene with methanolic sodium methoxide a t 28°C (14) indicates that conversion would he about 70% complete in experiment (1). This degree of conversion is quite adequate since 1,3,5-trinitrohenzene is the only product of the experiment. Conflicting K., values of 7700 1 mole-' (15) and 2260 1. mole-' (16) are available for the formation of the Meisenheimer intermediate from methyl picryl ether and methoxide ion in methanol at 2YC. These values can be applied in experiments (2) and (3), and even the lower figure indicates essentially con~plete conversions to the intermediates in these two experiments. Literature Cited (1) BUNNETT, J. F., Quart. Rev., 12, l(1958). (2) BUNNETT, J. F., Ann. Reu. Phys. Chm., 14 (1963). (3) Ross, S. D., Progress in Phys. Orgr. Chem., 1 (1963).
DE BRWN,C. A., AND VAN LEENT,F. H., Rec. Trau. Chim. Palls-Bas, 14, 144 (1895). (5) JACKSON, C. L., AND BOO$ W. F., Am. Chem. J . , 20, 444
(4) Loenv
(1898). (6) (7) (8) (9)
MEIGENHEIMER, J., Annalen, 323,205 (1902). CRAMPTON, M. R., AND GOLD,V., Chem. Cmnm., 256 (1965). C ~ M P T OM. N ,R., and GOLD,V., Chem. Corm., 549 (1965). CR.
