Page 820 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

Bromination has been shown not to exhibit a primary kinetic isotope effect in the 803
64
67
66
65
case of benzene, bromobenzene, toluene, or methoxybenzene. There are several
examples of reactants that do show significant isotope effects, including substituted SECTION 9.4
anisoles, 46 N,N-dimethylanilines, 68 and 1,3,5-trialkylbenzenes. 69 The observation of Specific Electrophilic
Substitution Reactions
isotope effects in highly substituted systems seems to be the result of steric factors that
can operate in two ways. There may be resistance to the bromine taking up a position
coplanar with adjacent substituents in the aromatization step, which would favor return
of the complex to reactants. In addition, the steric bulk of several substituents may
hinder solvent or other base from assisting in proton removal. Either factor could allow
deprotonation to become rate controlling.
Bromination is catalyzed by Lewis acids, and a study of the kinetics of bromination
of benzene and toluene in the presence of aluminum chloride has been reported. 70
Toluene is found to be about 35 times more reactive than benzene under these condi-
tions. The catalyzed reaction thus shows a good deal less substrate selectivity than the
uncatalyzed reaction, as would be expected on the basis of the greater reactivity of the
aluminum chloride-bromine complex.
Halogenation is also effected by acyl hypohalites, such as acetyl hypochlorite and
trifluoroacetyl hypobromite. 71

Cl 2 + Hg(O 2 CCH ) HgCl(O 2 CCH ) + CH CO Cl
2
3
3 2
3
Br 2 + Hg(O CCF ) HgBr(O CCF ) + CF CO Br
3
2
3 2
2
2
3
The latter is an extremely reactive species. Trifluoroacetate is a good leaving group
and facilitates cleavage of the O−Br bond. The acyl hypohalites are also the
active halogenating species in solutions of the hypohalous acids in carboxylic acids,
where they exist in equilibrium. Acetyl hypobromite is considered to be the active
halogenating species in solutions of hypobromous acid in acetic acid:
CH CO H+ HOBr CH CO Br + H O
3
3
2
2
2
This reagent can also be formed by reaction of bromine with mercuric acetate:
Hg(O CCH ) + Br 2 HgBr(O CCH ) + CH CO Br
3 2
2
2
3
2
3
Both of the above equilibria lie to the left, but acetyl hypobromite is sufficiently
reactive that it is the principal halogenating species in both solutions. The reactivity of
the acyl hypohalites as halogenating agents increases with the ability of the carboxylate
to function as a leaving group. This is, of course, correlated with the acidity of the
carboxylic acid. The estimated order of reactivity of Br ,CH CO Br, and CF CO Br is
3
2
3
2
2
64 P. B. D. de la Mare, T. M. Dunn, and J. T. Harvey, J. Chem. Soc., 923 (1957).
65
L. Melander, Acta Chem. Scand., 3, 95 (1949); Arkiv Kemi., 2, 211 (1950).
66
R. Josephson, R. M. Keefer, and L. J. Andrews, J. Am. Chem. Soc., 83, 3562 (1961).
67 J.-J. Aaron and J.-E. Dubois, Bull. Soc. Chim. Fr., 603 (1971).
68 J.-E. Dubois and R. Uzan, Bull. Soc. Chim. Fr., 3534 (1968); A. Nilsson, Acta Chem. Scand., 21, 2423
(1967); A. Nilsson and K. Olsson, Acta Chem. Scand., 23, 2317 (1969).
69
P. C. Myhre, Acta Chem. Scand., 14, 219 (1969).
70 S. Y. Caille and R. J. P. Corriu, Tetrahedron, 25, 2005 (1969).
71
(a) A. L. Henne and W. F. Zimmer, J. Am. Chem. Soc., 73, 1362 (1951); (b) P. B. D. de la Mare,
I. C. Hilton, and S. Varma, J. Chem. Soc., 4044 (1960); (c) P. B. D. de la Mare and J. L. Maxwell,
J. Chem. Soc., 4829 (1962); (d) Y. Hatanaka, R. M. Keefer, and L. J. Andrews, J. Am. Chem. Soc., 87,
4280 (1965); (e) J. R. Bennett, L. J. Andrews, and R. M. Keefer, J. Am. Chem. Soc., 94, 6129 (1972).