Page 836 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

Groups other than halogen can serve as leaving groups. Alkoxy groups are very 819
poor leaving groups in S 2 reactions but can act as leaving groups in aromatic
N
substitution. The reason is the same as for the inverted order of reactivity for the SECTION 9.5
halogens. The rate-determining step is the addition, and the alkoxide can be eliminated Nucleophilic Aromatic
Substitution
in the energetically favorable rearomatization. Nitro 129 and sulfonyl 130 groups can also
be displaced.

NO 2
NO 2
N SO Ph
O 2 2 + HN O N N
2
Ref. 131

NO 2 NO 2
CN + CH O – CN
3
NO 2 OCH 3
Ref. 132

The addition intermediates, which are known as Meisenheimer complexes, can
often be detected spectroscopically and can sometimes be isolated. 133 Especially in the
case of adducts stabilized by nitro groups, the intermediates are often strongly colored.

O –
CH O
Nu: – + CH O NO 2 3 N + Nu + O –
3
Nu – NO 2 CH 3
O
The range of nucleophiles that can participate in nucleophilic aromatic substi-
tution is similar to the range of those that participate in S 2 reactions and includes
N
alkoxides, 134 phenoxides, 135 sulfides, 136 fluoride ion, 137 and amines. 138 For reaction with
aromatic amines with 1-chloro-2,4-dinitrobenzene, the value of is −4 0, indicting
a substantial buildup of positive charge at nitrogen in the TS. 139 Substitution by
carbanions is somewhat less common. This may be because there are frequently

129
J. R. Beck, Tetrahedron, 34, 2057 (1978).
130 A. Chisari, E. Maccarone, G. Parisi, and G. Perrini, J. Chem. Soc., Perkin Trans. 2, 957 (1982).
131
J. F. Bunnett, E. W. Garbisch, Jr., and K. M. Pruitt, J. Am. Chem. Soc., 79, 385 (1957).
132
J. R. Beck, R. L. Sobczak, R. G. Suhr, and J. A. Vahner, J. Org. Chem., 39, 1839 (1974).
133 E. Buncel, A. R. Norris, and K. E. Russel, Q. Rev. Chem. Soc., 22, 123 (1968); M. J. Strauss, Chem.
Rev., 70, 667 (1970); C. F. Bernasconi, Acc. Chem. Res., 11, 147 (1978).
134
J. P. Idoux, M. L. Madenwald, B. S. Garcia, D. L. Chu, and J. T. Gupton, J. Org. Chem., 50, 1876
(1985).
135 R. O. Brewster and T. Groening, Org. Synth., II, 445 (1943).
136 M. T. Bogert and A. Shull, Org. Synth, I, 220 (1941); N. Kharasch and R. B. Langford, Org. Synth.,
V, 474 (1973); W. P. Reeves, T. C. Bothwell, J. A. Rudis, and J. V. McClusky, Synth. Commun., 12,
1071 (1982).
137
W. M. S. Berridge, C. Crouzel, and D. Comar, J. Labelled Compd. Radiopharm., 22, 687 (1985).
138 H. Bader, A. R. Hansen, and F. J. McCarty, J. Org. Chem., 31, 2319 (1966); F. Pietra and F. Del Cima,
J. Org. Chem., 33, 1411 (1968); J. F. Pilichowski and J. C. Gramain, Synth. Commun., 14, 1247 (1984).
139
T. M. Ikramuddeen, N. Chandrasekara, K. Ramarajan, and K. S. Subramanian, J. Indian Chem. Soc.,
66, 342 (1989).