Page 821 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

6
10 71b
e
804 1:10 :10 . It is this exceptionally high reactivity of the hypobromites that permits
them to be the reactive halogenating species in solutions where they are present in
CHAPTER 9
relatively low equilibrium concentration.
Aromatic Substitution
Molecular iodine is not a very powerful halogenating agent. Only very reactive
aromatics such as anilines or phenolate anions are reactive toward iodine. Iodine
monochloride can be used as an iodinating agent. The greater electronegativity of the
chlorine makes the iodine the electrophilic entity in the substitution reaction. Iodination
by iodine monochloride is catalyzed by Lewis acids, such as ZnCl . 72 Iodination can
2
also be carried out with acetyl hypoiodite and trifluoroacetyl hypoiodite. The methods
of formation of these reagents are similar to those for the hypobromites. 73
Direct fluorination of aromatics is not a preparatively important laboratory
reaction because it can occur with explosive violence. Mechanistic studies have been
done at very low temperatures and with low fluorine concentrations. For toluene, the
f and f m values are 8.2 and 1.55, respectively, indicating that fluorine is a very
p
unselective electrophile. The value in a Hammett correlation with + is −2 45.
Thus, fluorination exhibits the characteristics that would be expected for a very
reactive electrophile. 74 A number of reagents in which fluorine is bound to a very
electronegative group also serve as fluorinating agents, including CF OF, CF CO F,
2
3
3
75
CH CO F, and HOSO OF. The synthetic applications of these reagents are discussed
2
2
3
in Section 11.1.2 of Part B.
9.4.3. Protonation and Hydrogen Exchange
Hydrogen exchange resulting from reversible protonation of an aromatic ring can
be followed by the use of isotopic labels. Either deuterium or tritium can be used
and the experiment can be designed to follow either the incorporation or the release
of the isotope. The study of the mechanism of electrophilic hydrogen exchange is
somewhat simplified by the fact that the proton is the active electrophile. The principle
of microscopic reversibility implies that the TS occurs on a symmetrical potential
energy surface, since the attacking electrophile is chemically identical to the displaced
proton. The TS involves partial transfer of a proton to (or from) a solvent molecule(s)
to the aromatic ring. The intermediate complex is a cyclohexadienylium cation.
Partial rate factors for exchange for a number of substituted aromatic compounds
have been measured. They reveal activation of ortho and para positions by ERGs. Some
typical data are given in Table 9.8. The k /k benz ratio of around 300 indicates consid-
tol
erable substrate selectivity. The f value for toluene varies somewhat, depending on
p
2 76
the reaction medium, but is generally about 10 . The value for hydrogen exchange
in H SO -CF CO H-H Ois −8 6. 77 A similar value of −7 5 has been observed in
2 4 3 2 2
78
aqueous sulfuric acid. As seen for other electrophilic aromatic substitution reactions,
+
the best correlation is with . These values put protonation in the intermediate
range of selectivity.
72 R. M. Keefer and L. J. Andrews, J. Am. Chem. Soc., 78, 5623 (1956).
73
E. M. Chen, R. M. Keefer, and L. J. Andrews, J. Am. Chem. Soc., 89, 428 (1967).
74 F. Cacace, P. Giacomello, and A. P. Wolff, J. Am. Chem. Soc., 102, 3511 (1980).
75
A. Haas and M. Lieb, Chimia, 39, 134 (1985).
76
L. M. Stock and H. C. Brown, Adv. Phys. Org. Chem., 1, 35 (1963).
77 P. Rys, P. Skrabal, and H. Zollinger, Angew. Chem. Int. Ed. Engl., 11, 874 (1972).
78
S. Clementi and A. R. Katritzky, J. Chem. Soc., Perkin Trans. 2, 1077 (1973).