Textbook Errors, 68 GUEST AUTHOR Addison Ault
Cornell College Mt. Vernon, Iowa
The Activating Effect of Fluorine in Electrophilic Aromatic Substitution
T h e electrophilic substitution reactions of henzene and of henzene derivatives is a topic which is discussed in practically every introductory organic text.' One of the features of these reactions which is usually considered is that of the effect of a suhstituent atom or group upon the rate of the reaction and upon the relative amounts of the isomeric products. The substituent will cause the compound to react faster or slower than henzene itself (thereby being described as "activating" or "deactivating" respectively), and will influence the relative amounts of substitution ortho, meta, and para to itself. If more than the statistical amount of meta product (4070) is formed, the substituent is said to he meta directing; otherwise it is said to he ortho-para directing. If suhstituents are classified according to these criteria, they will he found to fall into three classes: activating and ortho-para directing, deactivating and ortho-para directing, and deactivating and meta directing; no suhstituent is known which is activating and meta directing. The halogens, including fluorine, are usually classified as deactivating and ortho-para directing. It is here demonstrated, however, that in certain electrophilic aromatic substitution reactions fluorine is actually an activating suhstituent. I t is usual for the two effects of a substituent to he treated as being independent of one another, hut in many cases this is not the most appropriate approach. At the present time it appears that there are two most important mechanisms for electrophilic aromatic substitution (1, Z), and that almost all such reactions involve a mechanism which is similar to one or the other of these. One mechanism involves a rate-determining attack of the electrophile on the pi electrons of the ring to form a "pi complex." This may he followed by any one of several different fast steps to form the several possible isomeric products. The second mechanism involves, as the rate-determining step, the formation of a "sigma complex" which can go on to give only one of the possible isomeric products. The key point of difference between these two mechanisms is that while in the former the rate-determining step is prior to (and independent of) the product-determining steps, in the
latter the several isomeric products are considered to he formed via competing rat,e-determining steps. I n the case of electrophilic aromatic substitution reactions involving a mechanism of the first type, it is necessary to separate the effect of the substituent upon the rate of reaction from the effect upon the product distribution. However, in the case of reactions involving a mechanism of the second type, this separation is not appropriate and may he misleading, as will he shown in some reactions where a fluorine atom is the suhstituent. The question of which mechanism is operative in a given reaction is not easily answered. However, it would appear that in reactions in which the electrophilic reagent displays a relatively small degree of selectivity toward different aromatic substrates (reactions involving "strong electrophiles"), the mechanism is likely to be of the first type, and that in reactions in which the selectivity of the electrophile is great the mechanism is likely to he of the second type (1). Examples of the former include nitration by nitronium salts (S,4,5) and possibly by nitric acid under certain conditions (6), hromination catalyzed by ferric chloride (7, 8), chlorination catalyzed by ferric chloride or aluminum chloride (9),and certain Friedel-Crafts alkylations (1, 10, 11, it, 13). Examples of the latter include uncatalyzed bromination (If+), uncatalyzed chlorination (15, 16), and certain Friedel-Crafts acetylations (17, 18, 19). I n reactions with mechanisms of the second type, where the isomeric products are considered to he formed via competing reactions, the analysis of the effect of the substituent is properly made in terms of partial rate factors. The partial rate factor is a statement of the rate of reaction to form each isomeric product, taking the rate a t a single position of henzene as unity. For example, in the chlorination of toluene by molecular chlorine in acetic acid at 25"C, the rate of substitution of toluene is 344 times greater than that of benzene, and the product distribution is 59.8y0 ortho-, 0.5% meta-, and 39.7y0 para-chlorotoluene (16). The partial rate factor for substitution into the ortho position is then 344 multiplied by the fraction of the ortho isomer in the product, times three, a statistical factor which takes into ncronnt, the fact that there are three times as manv positions for substitution in benzene as ortho positions in toluene. The meta and para partial rate factors are calculated analogously, using three and six respectively as the statistical factors. The resulting partial rate factors are: ortho 617, meta five, and para 820, indicating that the metyl group activates the ortho and para positions far more than the metaposition. With this background, we will now consider the effect ~~
Manuscripts for this column, or suggestions of material suitable for it, me rarely solicited. These should be sent with as many details as possible, and partieulrdy with references to modern textbooks, to W. H. Eberhwdt, Department of Chemistry, Georgia Institute of Technology, Atlanta, Georgia 30332. 'Since the purpose of this column is to prevent the spread and continuation of errors and not to evaluate individual texts, the source of erran discussed will not be cited. To he presented, the error must ocmr in at least two independent standard hooks.
Volume 43, Number 6, June 1966
/
329
of the fluorine atom as a suhstituent on electrophilic aromatic suhstitution reactions. I n many discussions of these reactions, a statement similar to the following is made: "a halogen atom deactivates the ring, but is ortho-para directing," and fluorine is typically included with the other halogens. Although the rate of substitution of fluorohenzene has always been found to be less than that of benzene,%the partial rate factor for suhstitution into the para position has often been found to be greater than unity (see Table 1). It is assumed, of
Table 1
Reaction
Partial rate Total factor for rate Percent substitution (be* ~ a r a into ~ a r a Referzene = 1). &oduct ~Osition. ence .
.~
Bromination: ca. 0 . 4 Br*; AIBn; CS.; 54-57" ,736 Chlorination: Cla; 60% HOAc;
--
~
~
~
89.1
2.1
(81)
89.1
3.93
(16)
1.51
(17)
'7h0
Acetylation: AcCl; A1C18; C1CH2CH2C1;
,252
100
-"
'7.6'
Acetylation: ACZO;AICln; CHsN02: 25' Tritium exchange: CFaCOOH (83.40%); H.0 (1.98%); HzSOn (14.62%); 25' Bromination of 2,3,5,6-Tetramethylfluorobenzene: (Dm Bra; HOAc; 309 For further data on the electrophilic suhstitution reactions of fluorobenzene and pfluorobenaene derivatives see Reference (84) (in which three other examples of a c t i d i o n by a parafluorine atom are cited) and References (3, 6, 8, 9, 11, 13, 18, o n d -14) "?
. A
Partial rate factor far substitution into the para position = (total rate relative to benzene) (fraction of the product which has para orientation) (6).
course, that the reactions cited in Table 1 involve a mechanism of the second type and thus are suitable for analysis in terms of partial rate factors. In these cases the fluorine atom is seen to activate the para position rather than to deactivate it. This phenomenon has been explained in terms of a release of electron density, through resonance, to the para position which more than compensates for the expected inductive withdrawal of electron density. The fact that para-fluorophenyldimethylcarbinyl chloride solvolyses more rapidly than the unsubstituted compound has also been interpreted in this manner (85). Thus the generabation that halogens are "ortho-para directing hut deactivating" must be qualified since in several electrophilic aromatic suhstitution reactions fluorine is seen to activate the position para to it.%
For an apparent exception, see Reference (80); compase, however. Reference (16). ~ h e i esppean td be a similar exception in a bromination of chlorobenzene (81).
330
/
Journal of Chemical Education
The exceptional effect of the fluorine atom has been made more apparent through an analysis of rate and product distribution data in terms of partial rate factors. However, as indicated above, one must not apply this kind of analysis indiscriminately. For example, fluorobenzene is nitrated by nitronium fluorohorate in tetramethylene sulfone a t 25°C at a rate equal to 0.45 that of benzene to give 8.5% ortho- and 91.5% para-nitrofluorobenzene (6). Calculation of a partial rate factor for substitution into the para position would give a value of 2.44, implying that the para position is substituted more readily than a position in benzene in this case also. However, toluene is nitrated under the same conditions only 1.67 times faster than benzene, indicating that the electrophilic reagent is very nonselective. Also, the fact that this reaction gives a yield of only 2.8% meta-nitrotoluene would give a calculated partial rate factor of 0.14 for nitration in the meta position, implying a deactivating effect of the methyl group which would be quite difficult to rationalize (4). These data are preferably interpreted in terms of a mechanism of the first type (4), for which an analysis in terms of partial rate factors is not appropriate.
Literature Cited (1) OLAH,G. A., FLOOD, S. H., KUHN,S. J., MOFFATT, M. E., and OVERCHUCK, N. A,, J . Am. Chem. Soe., 86, 1046 (19fi41. ~ - ~ ~ - , . (2) BERLINER, E., in "Pmgress in Physical Organic Chemistry," Interscience Publishers, (a division of John Wiley & Sons, Inc.), New York, 1964, Volume2, pp. 253321, (3) OLAH,G. A., AND KUHN,S. J., J. Am. Chem. Sac., 84, 3684 (1962). (4) OLAII,G. A., KUHN,S. J., AND FLOOD, S. H., J.Am. Chm. Sac., 83,4571 (1961). (5) Zbid, 4581 (1961). S. H., AND EVANS, J. C., (6) OLAH,G. A., KWN, S. J., FLOOD, J. Am. Chen. Soe., 84,3687 (1962). (7) OLAH,G. A., KUHN,8. J., FLOOD.S. H., AND HARDIE, B. A., J . Am. Chm. Sac., 86,1039 (1964). (8) Ibid., 1044 (1964). (9) OLAII,G . A., KUHN,S. J., AND HARDIE,B. A,, J . Am. Chm. Soc.. 86.1055 (19641. OLAH,'G. A.,KUHN, S. J., AND FLOOD, S. H., J. Am. Chem. Soc., 84,1688 (1962). Ibid., 1695(1962). M. E., J. Am. OLAH,G. A., FLOOD,S. H., A N D MOFPATT, Chm. Sac., 86,1060 (1964). I b i d , 1065 (1964). BROWN, H. C., A N D STOCK,L. M., J. Am. Chem. Soe., 79, 1421 (1957b (151 Ibid.. 5175 (1957). . , STOCK,L. M., AND BAKER,F. W., J. Am. Chem. Soc., 84,1661 (1962). BROWN,H. C., AND MARINO,G., J. Am. Chem. Soc., 84, 1658(1962). OLAH,G. A., MOWFATT, M. E., KUAN,S. J., AND HARDIE, B. A., J. Am. Chem. Sm., 86,2198 (1964). OLAE,G. A., KUHN,S. J., FLOOD,S. H., AND HARDIE,B. A,, o p . cit., 2203 (1964). DE LA MARE,P. B. D., AND ROBE~TSON, P. W., J . C h a . Sac., 1948,100. L. N., G ~ N E RA., Y., AND MACK,J. L., J . FERGUSON, Am. C h a . Sac., 76,1250 (1954). C., AND TAYLOR, R.,J.them. SOL,1961,2388. EABORN, ILLUMINATI, G., AND MARINO,G., J. Am. C h a . Sac., 78, 4975 (1956). ' STOCK,L. M., 4ND BROWN, H. C., J. Am. Chem. Soe., 84, 1668(1962). Y., AND HAM,G., J . Am. Chem. (25) BROWN; H. c., OKAMOTO, Soc., 79, 1906 (1957); O ~ M O T O Y.,, INUKAI, T., AND BROWN, H. C., J.Am. Chem. Soc., 80,4972 (1958).
