electron capture have been extensively studied by EPR
spectroscopy at 77 K.2d,9 To determine if spectra could be
obtained by use of other N-centered nucleophiles, the tert-
butoxide-promoted reaction of p-anisidine with 1 in DMSO
was examined. A very similar EPR spectrum was obtained
[a(N) ) 10.2, a(2H) ) 3.3, a(2H) ) 1.0, plus small
unresolved hfs], which we attribute to an analogous coupled
radical anion.
Scheme 1. SRN1 Reaction of Aryloxy Anions with
R,p-Dinitrocumene
The lifetimes of both O-coupled (4) and the N-coupled
(9) radical anions would probably be long enough for them
to be spectroscopically detected. First, because the unpaired
spin is localized in the nitroaromatic ring and second, because
EPR spectra of many diverse persistent analogues, including
nitroaromatic radical anions containing â-alkoxy substituents
as well as â-aminyl substituents, have been reported.10 The
fact that only the N-coupled variety could be detected by
EPR spectroscopy in our tert-butoxide-promoted reactions
is most probably related to differences in their rates of
formation. The relative reactivities of 6b and 7 were
estimated from competition experiments in which excess
quantities of the two nucleophiles were reacted with 1 and
the amounts of the two substitution products were deter-
mined. This showed that the 4-aminophenol (7) reacted more
than 100 times as fast as 4-methoxyphenol. Relative reac-
tivities determined competitively in this way are a measure
of the relative rates of coupling of nucleophiles with the
4-nitrocumyl radical (3).11,12,13 This coupling reaction is
known to occur near the diffusion-controlled limit for many
nucleophiles,11,12 and hence the observed difference in
reactivity suggests that the oxanion (6b) coupling with 3 may
be much slower. This may account for the lack of EPR
spectra with the oxanions.
There are several possible ways in which formation of
product 10 and radical anion 9 could be accounted for. First,
the initial oxanion 8 (Scheme 2) could be transformed to
the N-centered tautomer by proton transfer and, although 8
will be in large excess, if the N-centered anion reacts much
more rapidly with 3 this could explain the formation of 9. If
this possibility were correct, then it seems probable that the
m-isomer 6d should also yield N-coupled product; contrary
to what was observed. Second, 9 could be formed by direct
N-coupling of oxanion 8 and 3 followed by tautomerization.
However, we are not aware of other examples of direct
coupling of 8 through N according to this second possibil-
ity.14 Third, 8 could couple with 3 to give the O-coupled
product which then rearranges in some as yet unknown way
to afford 9. This seems unlikely because there is no evidence
of O-coupled products being unstable, and none was detected
in reactions carried out over times ranging from 1 min to 48
EPR spectroscopy. The reactants were mixed under nitrogen
in a quartz capillary tube which was immediately placed in
the resonant cavity of the spectrometer; however, no signals
developed.
The tert-butoxide induced reaction of 4-aminophenol (7)
with 1 was expected to produce the analogous ether product
because the hydroxyl hydrogen is at least 10 pK units more
acidic than the amino hydrogens.5 Treatment of 1 and freshly
purified 4-aminophenol with KOBu-t, under identical reac-
tion conditions, led to a very rapid reaction from which 92%
of the substitution and 3% of the elimination product were
isolated. Surprisingly, however, the substitution product
proved to be the amine 10 rather than the anticipated ether.
In separate reactions carried out over times ranging from 60
s to 48 h, yields of 10 were always g 85%. This indicated
that 10 was inert under the reaction conditions.
When the reaction was monitored by EPR spectroscopy a
well-resolved, although slightly anisotropic, spectrum was
obtained immediately on mixing (within 60 s) which
persisted for several hours before all signals disappeared.
This spectrum contained two components and the major one
was well matched by a computer simulation with the
following hyperfine splittings (hfs): a(N) ) 10.6, a(2H) )
3.34, a(2H) ) 1.2, a(N) ) 1.2 G (see Supporting Informa-
tion). The EPR spectra of radical anions derived from
nitrobenzene,6 4-nitrocumene,7 and related nitroaromatics
display hfs of very similar magnitudes for N and the two
sets of ring hydrogens, and hence we assign our spectrum
to the radical anion 9. The fact that a small hfs from an
additional N was observed confirmed that the nucleophile
was attached via the NH group in the radical anion. Our
EPR spectroscopic observations of such coupled radical
anions during SRN1 reactions in solution is unique, apart from
three-line nitroxide spectra reported by Tamura et al.8 Radical
anions derived from 4-nitrocumyl and related systems by
(8) Tamura, R.; Yamawaki, K.; Azuma, N. J. Org. Chem. 1991, 56,
5743-5745. Tamura, R.; Kohno, M.; Utsunomiya, S.; Yamawaki, K.;
Azuma, N.; Matsumoto, A.; Ishii, Y. J. Org. Chem. 1993, 58, 3953-3959.
(9) Symons, M. C. R.; Bowman, W. R. J. Chem. Soc., Perkin Trans. 2
1988, 583-589.
(10) Berndt, A. In Lando¨lt Bornstein, Magnetic Properties of Free
Radicals; Fischer, H., Hellwege, K.-H., Eds.; Springer: Berlin, 1980; Vol.
9d1, pp 430-678.
(5) Bordwell, F. G. Acc. Chem. Res. 1988, 21, 456-463. The pKas of
phenol, 4-aminophenol, and aniline in DMSO are 18.0, 19.7, and 30.6,
respectively.
(6) Gross, J. M.; Barnes, J. D.; Pillans, G. N. J. Chem. Soc. A 1969,
109-112.
(7) McKinney, T. M.; Geske, D. H. J. Am. Chem. Soc. 1967, 89, 2806-
2813. Terabe S.; Konaka, R. J. Am. Chem. Soc. 1973, 95, 4976-4986.
(11) Bunnett, J. F.; Galli, C. J. Am. Chem. Soc. 1981, 103, 7140-7147.
(12) Amatore, C.; Otturan, M. A.; Pinson, J.; Save´ant, J.-M.; Thiebault,
A. J. Am. Chem. Soc. 1985, 107, 3451-3459.
(13) Galli, C.; Gentili, P. Acta Chem. Scand. 1998, 52, 67-76.
(14) Treatment of 8 with acetic anhydride under these reaction conditions
gave only O-acetylation products.
828
Org. Lett., Vol. 2, No. 6, 2000