Page 1063 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

The synthetic value of the S 1 substitution reaction was developed from this 1047
RN
mechanistic understanding. The reaction is capable of providing highly substituted
carbon skeletons that would be inaccessible by normal S 2 processes. For example, SECTION 11.6
N
tertiary p-nitrocumyl halides can act as alkylating agents in high yield. The nucleophile S RN 1 Substitution
Processes
need not be a nitroalkane anion, but can be anions such as thiolate, phenolate, or
a carbanion such as those derived from malonate esters. 206 The same mechanism
operates as for the nitronate anion. Furthermore, the leaving group need not be a halide.
Displacement of nitrite ion from ,p-nitrocumene occurs with good efficiency. 207

CH 3 CH 3 CH 3
–
O N C NO 2 + (CH ) CNO 2 O N C C NO 2
2
2
3 2
CH CH
CH 3 3 3
95%
Azido, sulfonyl, and quaternary nitrogen groups can also be displaced by this
mechanism.
An S RN 1 mechanism has been proposed for the alkylation of amines by
p-nitrocumyl chloride. 208 209

CH
3 CH 3
O 2 N C Cl + N O 2 N C N+ Cl –
CH CH
3 3

Clearly, the tertiary nature of the chloride would make a S 2 mechanism highly
N
unlikely. Furthermore, the nitro substituent is essential to the success of these reactions.
Cumyl chloride itself undergoes elimination of HCl on reaction with amines.
A related process constitutes a method of carrying out alkylation reactions to give
highly branched alkyl chains that cannot easily be formed by an S 2 mechanism. The
N
alkylating agent must contain a nitro group and a second EWG. These compounds
react with nitronate anions to effect displacement of the nitro group. 210
–
R C NO 2 + R′ CNO 2 R C CR′ 2
2
2
2
Z Z NO 2
C H , CR, NO
Z = CN, CO 2 2 5 2
O
When radical scavengers are added, the reaction is greatly retarded, which indicates
that a chain reaction is involved. The mechanism shown below indicates that one of
the steps in the chain process is an electron transfer and that none of the steps involves
206
N. Kornblum, T. M. Davies, G. W. Earl, N. L. Holy, R. C. Kerber, M. T. Musser, and D. H. Snow,
J. Am. Chem. Soc., 89, 725 (1967); N. Kornblum, L. Cheng, T. M. Davies, G. W. Earl, N. L. Holy,
R. C. Kerber, M. M. Kestner, J. W. Manthey, M. T. Musser, H. W. Pinnick, D. H. Snow, F. W. Stuchal,
and R. T. Swiger, J. Org. Chem., 52, 196 (1987).
207 N. Kornblum, T. M. Davis, G. W. Earl, G. S. Greene, N. L. Holy, R. C. Kerber, J. W. Manthey,
M. T. Musser, and D. H. Snow, J. Am. Chem. Soc., 89, 5714 (1967).
208
N. Kornblum and F. W. Stuchal, J. Am. Chem. Soc., 92, 1804 (1970).
209 W. R. Bowman, Chem. Soc. Rev., 17, 283 (1988).
210
N. Kornblum and S. D. Boyd, J. Am. Chem. Soc., 92, 5784 (1970).