NMR Analysis of Product Mixtures in Electrophilic Aromatic Substitution Mary Ann Clark, Glenn Duns, Danny Golbergl, Anna Karwowska, Andree Turgeon, and Jolanda Turley John Abbott College, Ste. Anne de Bellevue, PO, Canada I t is well established that substituents on a benzene ring not only direct the position of subsequent substitutions but also affect the degree to which the substitution will occur. In a recent article in this Journal, Zaczek and Tyszkiewicz described an experiment to illustrate the relative activating ability of acetamido, alkoxy, and amino groups toward bromination of the benzene ring.z This experiment was presented to the authors (of this manuscript) as a problem-solving laboratory exercise using the approach devised by Harold Wil~on.~ Note: All procedures and safety aspects regarding the experiment carried out are described in detail in the Zaczek and Tyszkiewicz article. I t was found that the acetamido- and amino-substituted aromatics behaved as reported, producing mono-bromo and tri-hromo compounds, respectively. However, the product of the reaction with anisole gave a lower melting point than expected. NMR analysis i f the product (carried out in a CDCh solvent) revealed that a mixture had been produced and that the composition of the product could be determined through careful integration of the spectrum. Such product analysis adds an interesting feature to this laboratory exercise. Two singlets corresponding to the three hydrogens of the methoxy group appear near 6 4.0 (ppm), a facet confirming that a mixture of two oroducts had been obtained. Inteeration of the two peaks'indicates that one product predominates in a five-to-one ratio over the other (mole fraction of the major component = 0.84; that of the minor component = 0.16). These products could be any combination of mono-, di- or tri-substituted bromo anisoles, though melting point of the mixture suggested a mono- and di-substituted mixture had been obtained. Further qualitative observations of the NMR spectrum revealed that the methoxy group hydrogens of the major component of the mixture were shifted farther downfield than those of the minor product, an observation that sueeested that the maim com~onentwas a more substituted c G p o u n d (since bromine deshields the hydroreauired confirmation. confirma-eens). . These hvnotheses .. tion done using mole fraction analysis of the NMR spectrum. This technique uses the ratio of "the integration of the aromatic hydrogens" compared with "the integration of the methoxy region divided by three" (since there are three hydrogens in amethoxy group) to identify the mixture, since this ratio value corresponds to a weighted average of the number of ring hydrogens from the two components of the mixture, i.e.
Integration of the aromatic region (Integration of methoxy region113 802
-
(Molefraction X # of aromatic hydrogens of the major product)
+
(Mole fraction X # of aromatic hydrogens of the minor product)
Journal of Chemical Education
Theoretical Ratlo of "lntegratlon of Aromatlc Reglon"l"lniegratlon
of Methoxy Reglonl3" for Product Mlxtures from the Bromlnatlon of Anlsole Maim Froduct*
mono-bromo mono-bramo dl-bromo dl-bromo dl-bromo
Minor Product
Theoretlcsl Ratio
mono-bromo
dl-bromo mono-bromo dl-bromo
tri-bromo
uct* will be completely converted to di-bramo praducts before any ni-bromo compound forms. lCb~eOt10 BXperimenBl value of 3.43.
The theoretical ratio will vary significantly for different combinations of mono-, di-, and tri-brominated compounds; therefore, the products obtained may be determined by comparing the theoretical ratio to the actual ratio observed. In the anisole reaction, the major product was predicted to be 2,4-dibromoanisole, and the minor p-bromoanisole. These predictions were based upon such considerations as the o r t h ~ p a r directing a effect of the methoxy group, steric hindrance at the ortho position due to the presence of methoxy groups, as well as the qualitative NMR analysis oreviouslv described. The experimental ratio observed for mixture was 3.43 756mrn/(49mm/3)]. Of the calthe culated theoretical ratios, that of the predicted product mixture corresponds closest to the experimental ratio. The table summarizes the theoretical ratios for different product mixtures. (Note: 2,6-dihromo and/or o-bromo products could be substituted for their 2,4-dibromo and/or p-bromo counterparts, respectively, and still yield the same ratio values, but steric hindrance from the methoxy groups precludes these noaaihilities. r...--~-~~~~Similar "common-sense" areuments should be applied to other product mixture combinations.) In summary, use of mole fraction analysis permits precise quantitative product mixture analysis, a large improvement over qualitative and semiquantitative techniques. ~
Acknowledgment The authors would like to thank Harold Wilson, whose unique approach to teaching chemistry has given us the opportunity and ability to solve lab problems and has instilled in all of us a love for the subject. Our thanks also to Barbara McMahon for her invaluable assistance.
' Correspondence should oe addressed to D. Goloerg, 157 Bexni I Drive, Beaconsf.eld.PQ. Canada d9W 3A6. Zaczek, h M.; TysrKiewicr. R . 6. J. Chsm Educ. 1986, 63. 510 W lson. H. J. Chem. Educ. 1986, 63.484.
