Th e Th er m a l Rea ction of Ster ica lly
Hin d er ed Nitr oxyl Ra d ica ls w ith Allylic
a n d Ben zylic Su bstr a tes: Exp er im en ta l
a n d Com p u ta tion a l Evid en ce for Diver gen t
Mech a n ism s
SCHEME 1. Alk oxya m in e Der iva tives Syn th esized
by th e Rea ction of Nitr oxyl Ra d ica ls w ith Ben zylic
Su bstr a tes
J oseph E. Babiarz, Glen T. Cunkle,
Anthony D. DeBellis,* David Eveland,
Stephen D. Pastor,* and Sai P. Shum
Ciba Specialty Chemicals Corporation,
5
40 White Plains Road, P.O. Box 2005,
Tarrytown, New York 10591
Received J une 24, 2002
Abstr a ct: The reaction of stable sterically hindered nitroxyl
radicals with benzylic and allylic substrates was investi-
gated. An allyloxyamine derivative was obtained by the
reaction of 2 molar equiv of a nitroxyl radical with an
unactivated alkene. Experimental and computational evi-
dence is consistent with a low-energy pathway involving
addition of the nitroxyl radical to the double bond followed
by H-atom abstraction from the intermediate by another
equivalent of nitroxyl radical.
of alkoxy radicals, J enkins observed the formation of a
product that was formally the cross-coupling of an allylic
cyclohexenyl radical with nitroxide. J enkins made the
8
Sterically hindered nitroxyl radicals, for example,
reasonable suggestion that this cyclohexenyl radical was
the result of allylic hydrogen atom abstraction by a
nitroxyl radical. In this paper we report experimental and
computational results that strongly suggest that the
hindered nitroxyl radicals 1a -c react with allylic sub-
strates by a stepwise addition:hydrogen-atom-abstraction
mechanism.
2
,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), are gen-
erally considered to be both kinetically and thermody-
namically stable free radicals that do not typically
undergo hydrogen atom abstraction reactions with hydro-
carbon substrates. Hydrogen-atom-abstraction reactions
of photochemically excited TEMPO and 4-hydroxy-2,2,6,6-
tetramethylpiperidine-N-oxyl, 1a , are known.1 Isolated
reports on thermally initiated hydrogen-atom-abstraction
reactions by sterically hindered nitroxyl radicals have
recently appeared. Hazeldine and co-workers reported
that bis(trifluoromethyl)nitroxide abstracts hydrogen
-3
The reaction of 1a -c with the benzylic substrates
a -c at 130-143 °C (reflux temperature or pressure
2
vessel) for 2-3 days gave good yields of the corresponding
alkoxyamine derivatives 3a -e and hydroxylamines
4a -c. The reactions were carried out with excess alkyl-
benzene as the reaction solvent. The products formed
are consistent with the previously established mechanism
for this reaction (rate determining benzylic hydrogen
atom abstraction by nitroxyl radical followed by trapping
of the benzylic radical with another mole of nitroxyl
4
atoms from various substrates including alkylbenzenes.
5
6
Scaiano and Opeida have reported on the mechanism
and kinetics, respectively, of the reaction of TEMPO with
benzylic substrates.
The reaction of alkoxy radicals with cyclic alkenes in
the presence of a nitroxyl trapping agent was reported
5
7
radical). The reaction of 1a with ethylbenzene at 133
by Busfield et al. In a control experiment in the absence
°
C gave a low yield of the corresponding alkoxyamine
(
1) Presented in part at the 221th National Meeting of the American
derivative 5 (6% recrystallized) and a greater than
theoretical yield of the corresponding hydroxylamine 4a .
This is consistent with the known decomposition of
Chemical Society, San Diego, CA, April 1-5, 2001; American Chemical
Society: Washington, DC, 2001; Abstract ORG 527.
(2) J ohnston, L. J .; Tencer, M.; Scaiano, J . C. J . Org. Chem. 1986,
5
3
1
1, 2806.
similar secondary benzylic alkoxyamine derivatives at
(3) Keana, J . F. W.; Dinerstein, R. J .; Baitis, F. J . Org. Chem. 1971,
the reaction temperature of this study.9 Attempts to
6, 209.
(
prepare a bis-adduct by the reaction of 2 equiv or more
of 1a with 2a (in melt) or 2b (chlorobenzene solvent)
4) (a) Banks, R. E.; Haszeldine, R. N.; J ustin, B. J . Chem. Soc. (C)
971, 2777. (b) Banks, R. E.; Choudhury, D. R.; Haszeldine, R. N. J .
Chem. Soc., Perkin Trans. 1 1973, 1092. (c) Banks, R. E.; Birchall, J .
M.; Brown, A. K.; Haszeldine, R. N.; Moss, F. J . Chem. Soc., Perkin
Trans. 1 1975, 2033.
(
(
(8) Bottle, S. E.; Busfield, W. K.; J enkins, I. D. J . Chem. Soc., Perkin
Trans. 2 1992, 2145.
(9) (a) Hawker, C. J .; Barclay, G. G.; Orellana, A.; Dao, J .; Devon-
port, W. Macromolecules 1996, 29, 5245. (b) Devonport, W.; Michalak,
L.; Malmstr o¨ m, E.; Mate, M.; Kurdi, B.; Hawker, C. J .; Barclay, G. G.;
Sinta, R. Macromolecules 1997, 30, 1929.
5) Connolly, T. J .; Scaiano, J . C. Tetrahedron Lett. 1997, 38, 1133.
6) Opeida, I. A.; Matvienko, A. G.; Ostrovskaya, O. Z. Kinet. Catal.
1
995, 36, 441.
7) Busfield, W. K.; Grice, D. L.; J enkins, I. E.; Thang, S. H. Aust.
J . Chem. 1991, 44, 1407.
(
1
0.1021/jo020426r CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/22/2002
J . Org. Chem. 2002, 67, 6831-6834
6831