Hydrogen-Atom Abstraction
4997 5010
with
a
6
31 G(d,p) basis set. For hydrogen-atom abstractions by
121, 7381 7388), because when the same compound was calibrated
with two different clocks, the older value provided a generally better
agreement between the neophyl-based measurement and that ob-
tained with 5-hexenyl or 2-methyl-2-(2-naphtyl)-1-propyl radical.
[21] R. Leardini, M. Lucarini, G. F. Pedulli, L. Valgimigli, J. Org. Chem.
1999, 64, 3726 3730.
[22] When the neophyl or 2-methyl-2-(2-naphtyl)-1-propyl radicals were
used as radical clocks, very small amounts of side products were
observed. Thus, in addition to the expected tert-butylbenzene and iso-
butylbenzene, or 2-tert-butylnaphtalene and 2-isobutylnaphtalene,
that represent the unrearranged and rearranged hydrocarbons of the
neophyl and MNP radicals, we also observed 1-phenyl-2-methylpro-
pene or 1-(2-naphtyl)-2-methylpropene as identified on the basis of
their mass spectra. These hydrocarbons are know to originate from the
disproportionation of the rearranged radical R',[19b] and as such, the
denominator in Equation (18) has been adjusted accordingly.
[23] M. J. Kamlet, J.-L. M. Abboud, M. H. Abraham, R. W. Taft, J. Org.
Chem. 1983, 48, 2877 2887.
hydroperoxyl, the hydrogen-bonded pre- and post-reaction complex
structures were also determined. Minima were verified by performing
vibrational frequency calculations. Vibrational frequencies were scaled by
0.9806 as suggested by Scott and Radom.[50] In general, the transition state
structures were found using the STQN algorithm of Ayala and Schlegel,[51]
with the OPT QST2 or OPT QST3 keywords in Gaussian-98.[52] In
some cases, a guess at the transition-state structure was obtained from a
failed QST2 calculation and used in a subsequent QST3 calculation. This
procedure was usually successful. Transition-state structures were verified
by the presence of a single negative vibrational mode corresponding to the
reaction path connecting reactants and products. Additional single-point
energy calculations were performed on all structures at the B3LYP/6
311 G(2d,2p) and MPW1K/6 31 G(d,p)[34] levels for comparison.
Acknowledgements.
[24] The bS values used in the regression were 0.31, 0.45, and 0.55 for
acetonitrile, ethyl acetate, and tert-butanol, respectively.
[25] D. V. Avila, K. U. Ingold, J. Lusztyk, W. H. Green, D. R. Procopio, J.
Am. Chem. Soc. 1995, 117, 2929 2930.
[26] L. Valgimigli, J. T. Banks, K. U. Ingold, J. Lusztyk, J. Am. Chem. Soc.
1995, 117, 9966 9971.
[27] C. Chatgilialoglu, S. Rossini, Bull. Soc. Chim. Fr. 1988, 298 300.
[28] C. Chatgilialoglu, K. U. Ingold, J. Lusztyk, A. S. Narzan, J. C. Scaiano,
Organometallics, 1983, 2, 1332 1335.
We thank Prof. Domenico Spinelli for helpful discussion and Dr. Luca
Zuppiroli for assistance with HRMS. This project was in part supported by
the University of Bologna and the MIUR Research project ™Free Radical
Research in Chemistry and Biology: Fundamental Aspects and Applica-
tions in Environment and Material Science∫. DAP thanks NSERC Canada,
Vanderbilt University and Professor Ned A. Porter for their support.
[29] C. K. Ingold, F. R. Shaw, J. Chem. Soc. 1927, 2918 2926.
[30] In principle, the results obtained by competition kinetics of this kind
might be affected by the hydrogen-atom exchange between the silane
and the 5-pyrimidinoxyl radical. If this reaction is fast enough it might
regenerate some 5-pyrimidinol [Eq. (39)], thus resulting in an under-
[1] a) L. J. Marnett, Carcinogenesis 2000, 21, 361 370; b) A. Sevanian, F.
Ursini, F. Free Radical Biol. Med. 2000, 29, 306 311; c) D. Steinburg,
S. Parhsarathy, T. E. Carew, J. C. Khoo, J. L. Witztum, N. Engl. J. Med.
1989, 320, 915 924; d) G. M. Chisholm, D. Steinburg, Free Radical
Biol. Med. 2000, 28, 1815 1826.
estimation of rate constant k21
.
[2] a) M. Lucarini, P. Pedrielli, G. F. Pedulli, S. Cabiddu, C. Fattuoni, J.
Org. Chem. 1996, 61, 9259 9263; b) M. Lucarini, G. F. Pedulli, M.
Cipollone, J. Org. Chem. 1994, 59, 5063 5070 and references therein.
[3] P. Franchi, M. Lucarini, G. F. Pedulli, L. Valgimigli, B. Lunelli, J. Am.
Chem. Soc. 1999, 121, 507 514.
[4] a) G. W. Burton, T. Doba, E. J. Gabe, L. Hughes, F. L. Lee, L. Prasad,
K. U. Ingold, J. Am. Chem. Soc. 1985, 107, 7053 7065; b) G. W.
Burton, K. U. Ingold, Acc. Chem. Res. 1986, 19, 194 201.
[5] J. S. Wright, E. R. Johnson, G. A. DiLabio, J. Am. Chem. Soc. 2001,
123, 1173 1183.
[6] See for example: J. Alanko, A. Riutta, P. Holm, I. Mucha, H.
Vapaatalo, T. Metsa-Ketela, Free. Radical Biol. Med. 1999, 26, 193
201; M. Manno, C. Ioannides, G. G. Gibson, Toxicol. Lett. 1985, 25,
121 130.
[7] J. S. Wright, D. A. Pratt, G. A. DiLabio, T. P. Bender, K. U. Ingold,
Cancer Detect. Prev. 1998, 22, 204.
[8] M. C. Foti, E. R. Johnson, M. R. Vinqvist, J. S. Wright, L. R. C.
Barclay, K. U. Ingold, J. Org. Chem. 2002, 67, 5190 5196.
[9] D. A. Pratt, G. A. DiLabio, G. Brigati, G. F. Pedulli, L. Valgimigli, J.
Am. Chem. Soc. 2001, 123, 4625 4626.
[10] H. Bredereck, F. Effenberger, H. E. Schweizer, Chem. Ber. 1962, 95,
803 809.
[11] A. Dornow, H. Hell, Chem. Ber. 1960, 93, 1998 2001.
[12] P. C. Unangst, D. T. Connor, C. R. Kostlan, G. P. Shrum, S. R. Miller,
G. Kanter, J. Heterocycl. Chem. 1995, 32, 1197 1200; D. T. Connor,
C. R. Kostlan, US Pat. 5,177,079, January 5, 1993.
[13] F. J. Walker, J. L. LaMattina, US Pat. 4,711,888 December 8, 1987.
[14] F. J. Walker, K. G. Kraus, J. Heterocycl. Chem. 1987, 24, 1485 1486;
J. L. LaMattina, C. J. Mularski, Tetrahedron Lett. 1984, 25, 2957 2960.
[15] M. Lucarini, P. Pedrielli, G. F. Pedulli, L. Valgimigli, D. Gigmes, P.
Tordo, J. Am. Chem. Soc. 1999, 121, 11546 11553.
k39
.
.
(Me3Si)3SiH PymO ! (Me3Si)3Si PymOH
(39)
To check the relevance of the reaction in Equation (39), the time-
dependence of the EPR signal of the photolytically generated
5-pyrimidinoxyl radical (PymO ) for compounds 5c and 5e was
.
followed both in the absence and in the presence of variable amounts
of TTMSS. From these experiments it could be concluded that for
both 5-pyrimidinols (and conceivably for any other reported in this
work) the rate constant of reaction is k39 < 1mÀ1 sÀ1 and can therefore
be neglected under our experimental conditions. One additional
source of error in the competition kinetics relying on the measurement
of the loss of starting material both for the compound under
investigation and the reference compound arises from side reactions
consuming one or both of the competing reactants. Since some of the
measurements herein reported were performed with starting concen-
trations of pyrimidinol comparable to the concentration of radical
initiator (di-tert-butylperoxide) and considering the relatively high
absorbance of 5-pyrimidinols in the UV spectral region corresponding
to the Hg-lamp emission (see Table 7) it is possible that direct
photolysis of the pyrimidinol occurs to some extent which would be
reflected in an overestimation of their rate of reaction with alkoxyl
radicals. We thank a referee for pointing this out. However it should
be noted that: 1) when benzene solutions of pyrimidinols 5c f were
irradiated directly in the cavity of an EPR spectrometer in the absence
of any radical initiator, incident radiations 50 100 times more intense
of those employed in the competition kinetics were necessary to
observe EPR signals due to the corresponding aryloxyl radicals
(presumably originated by photoionization followed by fast proton
transfer), while no signal could be observed for pyrimidinols 5a,b; 2)
kinetic measurement performed with different initial amounts of
[16] D. Griller, K. U. Ingold, Acc. Chem. Res. 1980, 13, 317 323.
[17] M. Newcomb, Tetrahedron 1993, 49, 1151 1176.
[18] C. Chatgilialoglu, K. U. Ingold, J. C. Scaiano, J. Am. Chem. Soc. 1981,
103, 7739 7742.
[19] a) J. A. Franz, R. D. Barrows, D. M. Camaioni, J. Am. Chem. Soc.
1984, 106, 3964 3967; b) A. Burton, K. U. Ingold, J. C. Walton, J. Org.
Chem. 1996, 61, 3778 3782.
[20] This value was preferred to the newer value of 4 Â 102 sÀ1 obtained by
Fischer and co-workers (M. Weber, H. Fisher, J. Am. Chem. Soc. 1999,
pyrimidinol (leading to
a different extent of direct photolysis)
afforded almost identical results; 3) kinetic measurements based on
this competitive approach were performed under identical exper-
imental conditions on a-tocopherol (for which direct photolysis is a
known process and which has an ionization potential lower than all of
the pyrimidinols) affording rate constants values very close to those,
previously reported (ref. [26]), obtained by laser flash photolysis
Chem. Eur. J. 2003, 9, 4997 5010
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5009