Bond dissociation energies of O-H bonds in substituted phenols from equilibration studies

Article abstract of DOI:10.1021/jo961039i

Bond dissociation energies (BDE) of several phenolic compounds have been determined by studying the equilibration of couples of phenols and of the corresponding phenoxyl radicals by means of EPR spectroscopy. Measurements were carried out in highly concentrated solutions submitted to continuous photolysis in the presence of di-tert-butyl peroxide. Since under this experimental condition the decay of the phenoxyl radicals was slower than the hydrogen transfer reaction from phenols to phenoxyls, equilibrium concentrations of the two radicals were actually measured. Due to the fact that the radical species are continuously generated in solution, phenols giving short-lived phenoxyl radicals could also be investigated by this method. All of the examined phenols are characterized by O-H bonds weaker than that of the parent compound, PhOH, and their BDE values can be calculated to a good approximation by an additive rule using fixed contributions for the various substituents. Only in the case of the sterically crowded 4-methoxytetramethylphenol (5b), where the p-methoxy substituent is compelled to stay out of the plane of the aromatic ring, is the experimental BDE remarkably different from the calculated value.

Full text of DOI:10.1021/jo961039i

J . Org. Chem. 1996, 61, 9259-9263
9259
Bon d Dissocia tion En er gies of O-H Bon d s in Su bstitu ted P h en ols
fr om Equ ilibr a tion Stu d ies
Marco Lucarini, Pamela Pedrielli, and Gian Franco Pedulli*
Dipartimento di Chimica Organica “A. Mangini” dell’Universita`,
Via S. Donato 15, I-40127 Bologna, Italy
Salvatore Cabiddu and Claudia Fattuoni
Dipartimento di Scienze Chimiche dell’Universita`, Via Ospedale 72, I-09124 Cagliari, Italy
Received J une 3, 1996 (Revised Manuscript Received October 23, 1996X)
Bond dissociation energies (BDE) of several phenolic compounds have been determined by studying
the equilibration of couples of phenols and of the corresponding phenoxyl radicals by means of
EPR spectroscopy. Measurements were carried out in highly concentrated solutions submitted to
continuous photolysis in the presence of di-tert-butyl peroxide. Since under this experimental
condition the decay of the phenoxyl radicals was slower than the hydrogen transfer reaction from
phenols to phenoxyls, equilibrium concentrations of the two radicals were actually measured. Due
to the fact that the radical species are continuously generated in solution, phenols giving short-
lived phenoxyl radicals could also be investigated by this method. All of the examined phenols are
characterized by O-H bonds weaker than that of the parent compound, PhOH, and their BDE
values can be calculated to a good approximation by an additive rule using fixed contributions for
the various substituents. Only in the case of the sterically crowded 4-methoxytetramethylphenol
(5b), where the p-methoxy substituent is compelled to stay out of the plane of the aromatic ring,
is the experimental BDE remarkably different from the calculated value.
In a previous paper, we reported the determination of
the O-H homolytic bond dissociation energies (BDE) in
four substituted phenols of particular interest as anti-
oxidants including R-tocopherol.1 The values of these
important thermochemical parameters were obtained by
measuring, by means of EPR spectroscopy, the equilib-
rium constant, K1, for the reaction between galvinoxyl
(G•) and each of these phenols (eq 1) using as reference
compound 2,4,6-tri-tert-butyl phenol whose BDE value
is known from calorimetric studies.2,3
81.24 kcal mol-1 value reported for 2,4,6-tri-tert-bu-
tylphenol,2 their absolute values depend on the accuracy
of the above measure and may be subject to changes.
A disadvantage of the above technique is that it can
hardly be applied to the determination of BDE values of
phenols affording by oxidation short-lived phenoxyl radi-
cals. In these cases mixing of the reactants leads to the
formation of radicals not surviving for the length of time
needed to record an EPR spectrum of the mixture. This
problem can be overcome by making use of the “radical
buffer” method originally proposed by Hiatt and Benson4
for the determination of the heats of formation of alkyl
radicals. The approach used in the present work is
similar to that described by Griller and co-workers5 and
consists of generating the equilibrating phenoxyl radicals
by continuous photolysis. It has the advantage with
respect to the procedure followed by Colussi et al.6 and
by J ackson et al.,7 who generated the phenoxyls by
reaction with galvinoxyl or diphenylpicrylhydrazyl, that
phenols giving very short-lived radicals can be investi-
gated as well.
G• + ArOH h GH + ArO•
(1)
The determination of K1 was straightforward when the
oxidation of the phenols, ArOH, reacting with galvinoxyl
gave highly persistent phenoxyl radicals that did not
decay appreciably during the recording of the EPR
spectrum of the reaction mixture. With other phenoxyls,
where the occurrence of other reactions such as reversible
formation of dimers or disproportionation caused slow
decay of the EPR signals, the equilibrium constants were
obtained by performing careful kinetic analyses of the
time evolution of the equilibrating species.
With respect to other techniques employed for the
determination of bond dissociation energies, the EPR-
based method presents the advantage of greater accuracy
since even relatively large errors in the measurement of
radical concentrations, and therefore, of K1, give rise to
small errors in the BDEs because of the logarithmic
relation connecting these two quantities. It should,
however, be emphasized that since the bond dissociation
energies obtained by this method are all referred to the
We report here the determination of the O-H bond
dissociation energies of phenols 1-6b.
Resu lts a n d Discu ssion
Ra d ica l Bu ffer . Bond dissociation energies are de-
termined by measuring the equilibrium constants for the
hydrogen transfer reaction (eq 5) taking place between
couples of phenols and of the corresponding phenoxyl
(4) (a) Hiatt, R.; Benson, S. W. J . Am. Chem. Soc. 1972, 94, 25-29;
(b) Int. J . Chem. Kinet. 1972, 4, 151-157; (c) 1973, 5, 385-396.
(5) Castelhano, A. L.; Griller, D. J . Am. Chem. Soc. 1982, 104, 3655.
(6) Coronel, M. E. J .; Colussi, A. J . Int. J . Chem. Kinet. 1988, 20,
749-752. Coronel, M. E. J .; Colussi, A. J . J . Chem. Soc., Perkin Trans.
2 1994, 785-787.
X Abstract published in Advance ACS Abstracts, December 1, 1996.
(1) Lucarini, M.; Pedulli, G. F.; Cipollone, M. J . Org. Chem. 1994,
59, 5063.
(2) Mahoney, L. R.; Ferris, F. C.; DaRooge, M. A. J . Am. Chem. Soc.
1969, 91, 3883.
(3) Mahoney, L. R.; Mendenhall, G. D.; Ingold, K. U. J . Am. Chem.
Soc. 1973, 95, 8610.
(7) J ackson, R. A.; Hosseini, K. M. J . Chem. Soc., Chem. Commun.
1992, 967.
S0022-3263(96)01039-0 CCC: $12.00 © 1996 American Chemical Society

9260 J . Org. Chem., Vol. 61, No. 26, 1996
Lucarini et al.
radicals. These are generated, within the cavity of an
EPR spectrometer, by continuous photolysis of deoxy-
genated benzene solutions containing two phenols (see
Figure 1), characterized by BDE values differing at most
by 2.5 kcal mol-1, and by the radical photoinitiator di-
tert-butyl peroxide. The overall reaction scheme is
described in eqs 2-8.
F igu r e 1. Room-temperature EPR spectra observed under
continuous irradiation of deoxygenated benzene solutions of
di-tert-butyl peroxide and (a) 4-methoxytetramethylphenol
(5b), (b) 2,6-di-tert-butylphenol (2b), and (c) a mixture of 5b
(0.12 M) and 2b (0.72 M).
BuOOBu
9
hν8 2BuO•
8 BuOH + Ar1O•
8 BuOH + Ar2O•
(2)
(3)
BuO• + Ar1OH
9
BuO• + Ar2OH
9
(4)
(5)
(6)
obtained, within experimental error, the same value of
the equilibrium constant for a given couple of compounds.
Further support for the assumption that reaction 5 is
faster than the decay of the equilibrating radicals is
provided by the values recently measured by Ingold and
co-workers8 of the rate constants for the hydrogen
transfer from some phenolic antioxidants to the phenoxyl
Ar1O• + Ar2OH yk5z Ar1OH + Ar2O•
k-5
2ArO• h dimers
radical, C6H5O•. This reaction has been found to be
kt
293K
2ArO• 98 products
(7)
(8)
unexpectedly fast with values of k5
as large as 1.1 ×
109 M-1 s-1 for R-tocopherol and 8.4 × 107 M-1 s-1 for
ubiquinol-10 in benzene solution. Also, the reactivity of
phenoxyl radicals toward hindered phenols is surpris-
ingly high; for instance, 4-methoxyphenoxyl in PhCl
abstracts the hydroxylic hydrogen of 2,4,6-tri-tert-bu-
tylphenol with a rate constant of 4.75 × 105 M-1 s-1 at
333 K.9 Given the radical concentration of ca. 10-5-10-6
M, and given the rate constant for the self-reaction of
4-methoxyphenoxyl of 3.4 × 107 M-1 s-1 in benzene,10 the
decay of the equilibrating species is computed to be more
than 2 orders of magnitude slower than the hydrogen
transfer reaction provided the initial concentrations of
the phenols are ca. 0.1 M or more.
dimers 98 products
The molar ratio of the two phenoxy radicals [Ar2O•]/
[Ar1O•] is obtained from the EPR spectra either by double
integration of appropriate lines or by comparison with
computer-simulated spectra when the lines from the two
species strongly overlap. The equilibrium constant, K5,
is determined by introducing in eq 9 the initial concen-
[Ar1OH][Ar2O•]
[Ar1O•][Ar2OH]
K5 )
(9)
When couples of phenols substituted at all para and
ortho positions were studied, the EPR measurements
were straightforward since clean and intense spectra of
the two phenoxyl radicals were usually obtained under
irradiation. On the other hand, with phenolic derivatives
lacking at least one ortho or para substituent, EPR
spectra of secondary radical species growing up with time
were almost invariably observed. These were dimeric
and polymeric aroxyls resulting from oxidation of the
head to tail combination product of the primarily formed
phenoxyls as exemplified in eq 10 for an ortho-substituted
trations of the phenols [Ar1OH]0 and [Ar2OH]0. In order
to ensure that at the time of measurement, i.e., a few
minutes after the start of irradiate the solution, no
significant phenol depletion has occurred, high concen-
trations of the reactants (0.1-1 M) were used.
Of course, this approach can only be applied if the
hydrogen transfer reaction (eq 5) takes place rapidly
relative to the decay of the phenoxyl (eqs 6-8), so that
the equilibrium concentrations of the two radicals are
actually measured. To check if this was the case,
different experimental conditions were employed by
changing either the initial absolute concentrations of the
phenols and their ratios or the rate of initiation by
partially cutting off the light with metal sectors of
different diameters or by changing the amount of added
peroxide. Actually, in each of these measurements we
(8) Foti, M.; Ingold, K. U.; Lusztyk, J . J . Am. Chem. Soc. 1994, 116,
9440-9447.
(9) Mahoney, L. R.; DaRooge, M. A. J . Am. Chem. Soc. 1975, 97,
4722.
(10) Weiner, S. A. J . Am. Chem. Soc. 1972, 94, 581. Mahoney, L.
R.; Weiner, S. A. J . Am. Chem. Soc. 1972, 94, 1412.

Bond Dissociation Energies of O-H Bonds
J . Org. Chem., Vol. 61, No. 26, 1996 9261
galvinoxyl1 is good (differences are 0.32, 0.21, and -0.70
kcal mol-1 for 4d , 4e, and 6b, respectively). With
R-tocopherol (6b) the difference, larger than in the other
two cases, could be due to the fact that in our previous
paper this compound was a commercial product used as
received. In fact, it has been recently shown by Bowry
and Ingold12 that commercial R-tocopherol contains a very
minor impurity that can accelerate the decay of the
R-tocopheroxyl radical; this might have resulted in a
miscalculation of the equilibrium constant for the reac-
tion of 6b with galvinoxyl. In the present case this
impurity was instead carefully removed before perform-
ing any measurement.13
A point worthy of comment is the magnitude of the
experimental error that becomes larger as the BDE
difference from the value of the chosen standard (81.24
kcal mol-1 for 4b) becomes greater. This is due to the
fact that direct equilibration with 4b could only be
performed with those phenols whose BDE values differ
by 2.5 kcal mol-1 at most from that of the standard (4b);
these, in turn, were used as reference substrates for
measuring the BDE’s of other phenols. Thus, a greater
number of steps required for a given determination
results in a larger experimental error.
E ffect of Su b st it u en t s on t h e Ar O-H Bon d
Str en gth s. Table 1 and its pictorial equivalent (Figure
2) show how important the number and the nature of
the substituents are in determining the strength of the
ArO-H bond in phenols; actually, the measured BDE
values span a range of 10 kcal mol-1 on passing from
phenol to R-tocopherol. All the substituents taken into
account in the present investigation produce a weakening
of the O-H bond by preferentially stabilizing the phe-
noxyl and/or destabilizing the phenol as the result of
electronic and steric factors.14-18 Thus, ortho-substituted
phenols are destabilized by the steric repulsion between
the hydroxyl group and the substituent, especially when
the latter is as bulky as a tert-butyl group.19 Electronic
factors are instead important in determining the O-H
bond strength in phenols containing substituents that
may conjugate with the aromatic system. Thus, electron-
donating substituents are expected to weaken the O-H
bond by a combination of effects, i.e., the destabilization
of the phenol (see structures B) and the stabilization of
the phenoxy radical due to the delocalization of the
unpaired electron in the substituent (D), while electron
acceptors are expected to stabilize both species (see B and
D).
Ta ble 1. Bon d Dissocia tion En er gies of Su bstitu ted
P h en ols
BDEcalc
BDEexp
/
(kcal
ArOH
R1
R2
R3
na (kcal mol-1
)
mol-1
)
1
H
H
H
H
H
H
H
H
H
H
H
CMe3
OMe
H
H
3
2
2
0
1
0
0
1
2
1
88.3 ( 0.8
86.2 ( 0.6
85.3 ( 0.5
87.6
85.9
85.7
83.2
84.1
82.8
83.7
86.6
86.7
82.4
80.9
79.3
81.1
78.4
79.2
78.7
78.7
78.7
1a
1b
1c
2a
2b
2c
3b
3c
4a
4b
4c
4d
4e
5a
5b
6a
6b
Me
CMe3
OMe
H
H
H
82.81 ( 0.21
84.50 ( 0.38
82.80 ( 0.21
83.16 ( 0.15
86.62 ( 0.26
86.7 ( 0.3
Me
CMe3
OMe
H
H
Me
CMe3
OMe
CMe3
CMe3
Me
H
H
Me
CMe3
OMe
Me
OMe
82.73 ( 0.18
H
H
H
H
81.24b
0
0
0
1
1
1
1
80.00 ( 0.12
81.02 ( 0.13
78.31 ( 0.13
79.20 ( .15
81.88 ( 0.20
78.25 ( 0.18
78.23 ( 0.25
H, Me OMe
Me OMe
Me
HPMC
R-tocopherol
a
The index n indicates if the BDE difference with respect to
tri-tert-butylphenol (4b) has been determined directly (0) or
through the intermediation of one (1), two (2), or three (3) other
b
phenols. Reference compound; see ref 2.
phenol. A study on the nature of these species has been
reported elsewhere.11
Since these secondary aroxyls are quite persistent, they
accumulate in solution and their spectra gradually
replace those of the transient primary radicals. Thus,
when performing equilibration studies, care had to be
taken to avoid misassignments of the EPR signals, and
the irradiated solutions were changed as often as pos-
sible.
It is also apparent from Table 1 that, similar to what
has been reported by other authors,15-17 the decrease of
the bond strength due to a given substituent is roughly
constant in the variously substituted phenols. By using
a multivariable minimization procedure we derived the
contribution, ∆BDE(X), for each group in the ortho, meta,
The measured bond dissociation energies for the ex-
amined phenolic compounds are reported in Table 1.
These values are indeed free energies rather than free
enthalpies for the dissociation reaction of the O-H bond.
Since, however, the entropic contribution to the free
energy change for the equilibration reaction 5 has been
found to be very small for several couples of phenols,1
the ∆S has been neglected in all cases.
(12) Bowry, V. W.; Ingold, K. U. J . Org. Chem. 1995, 60, 5456-
5467.
(13) Valgimigli, L.; Banks, J . T.; Ingold, K. U.; Lusztyk, J . J . Am.
Chem. Soc. 1995, 117, 9966.
(14) Burton, G. W.; Doba,T.; Gabe, E. J .; Hughes, L.; Lee, F. L.;
Prasad, L.; Ingold, K. U. J . Am. Chem. Soc. 1985, 107, 7053-7065.
(15) Bordwell, F. G.; Cheng, J .-P. J . Am. Chem. Soc. 1991, 113,
1736-1743. Bordwell, F. G.; Zhang, X.-M. J . Org. Chem. 1990, 55,
6078-6079.
(16) Bordwell, F. G.; Zhang, X.-M.; Satish, A. V. J . Am. Chem. Soc.
1994, 116, 6605-6610. Bordwell, F. G.; Zhang, X.-M. J . Phys. Org.
Chem. 1995, 8, 529-535.
(17) Lind, J .; Shen, X.; Eriksen, T. E.; Mere´nyi, G. J . Am. Chem.
Soc. 1990, 112, 479-482.
The reported data cover the range 78-88 kcal mol-1
,
the higher values being found for phenol, PhOH (88.3
kcal mol-1), and the lower one for R-tocopherol (78.23 kcal
mol-1). The agreement with the values previously re-
ported by us and determined by equilibration with
(11) Magnaterra, F.; Pedrielli, P.; Pedulli, G. F. Gazzetta 1996, 126,
673-677.
(18) Arnett, E. M.; Flowers, R. A. Chem. Soc. Rev. 1993, 9.
(19) Ingold, K. U. Can. J . Chem. 1962, 40, 111-121.

9262 J . Org. Chem., Vol. 61, No. 26, 1996
Lucarini et al.
Ta ble 2. Ad d itive Con tr ibu tion s (∆BDE/ k ca l m ol-1) for
Ca lcu la tin g th e BDE Va lu es in Su bstitu ted P h en olsa
substituent
ortho (two groups)
meta (two groups)
para
Me
CMe3
OMe
-3.5
-4.8
-3.9
-1.0
-1.0
-0.9
-1.7
-1.9
-4.4
a
The BDE value for phenol (87.6 kcal mol-1) to be used in eq
11 was also obtained by the minimization procedure employed to
derive the group contributions.
destabilization of the phenol by the para methoxy sub-
stituent are substantially reduced. The contribution of
the OMe group to the bond strength of 5b results to be
-1.2 instead of the -4.4 kcal mol-1 value reported in
Table 2. On the other hand, in 2,3,6-trimethyl-4-meth-
oxyphenol (5a ), differing from 5b only for the absence of
one of the two meta substituents, the calculated and the
experimental BDE values are coincident (79.20 kcal
mol-1) and much lower than in 5b (81.88 kcal mol-1).
This, of course, is due to the fact that, in 5a , the methoxy
group lies coplanar with the aryl ring and can therefore
conjugate with the aromatic π system.
An other point worthy of mention is that both HPMC
(6a ) and R-tocopherol (6b) show experimental BDE
values in good agreement with those calculated with the
additive rule of eq 11. This means that these two
compounds behave as a hypothetical 4-methoxytetra-
methylphenol where the methoxy substituent lies on the
plane of the aromatic ring; they adopt this geometry
particularly favorable to the conjugation between the
phenolic ring and the oxygen lone pair, because of the
presence of the condensed six-membered ring, as has
been widely discussed in the literature.6,7,14 These data
suggest that, from a thermodynamic point of view,
R-tocopherol has nothing special except the right struc-
ture to maximize the interactions responsible for weak-
ening the O-H bond.
F igu r e 2. Experimental bond dissociation energy values for
substituted phenols.
For phenolic compounds, containing ortho methyl
substituents, for which no direct determination was
known, Ingold and co-workers estimated the bond dis-
sociation energy values from the measured rate constants
for the reaction of the phenols with peroxy radicals (eq
12) by means of eq 13.
ROO• + ArOH
9
8 ROOH + ArO•
(12)
D[ArOH] (kcal/mol) ) 100.4 - 3.07 log(k12/M-1 s-1
)
(13)
Equation 13 implies that the BDE’s should vary
linearly with the logarithm of the rate constant k12. To
check this assumption, we plotted the bond strength
obtained in the present work against the log k12 values
reported for several ortho-disubstituted phenols.14 Figure
3 shows that the data lie on two straight lines: one for
the phenols containing methyl substituents and the other
for phenols containing tert-butyl substituents. The cor-
relation obtained in the former case and expressed by
eq 14 is rather good (r ) 0.987), and the derived
coefficients are reasonably close to those of eq 13, while
for the phenols ortho disubstituted with tert-butyl groups
the correlation is given by eq 15.
and para positions. These values are reported in Table
2, while the bond strengths calculated from them by
means of eq 11 are shown in the last column of Table 1.
BDE(C6H5-nXnOH) ) BDE(C6H5OH) +
n
∆BDE(X) (11)
∑
i
The agreement between experimental and calculated
BDE’s is reasonably good except for 4-methoxytetra-
methylphenol (5b), where the bond strength is 3.2 kcal
mol-1 larger than the calculated value. This discrepancy
is certainly due to an anomalous behavior of the 4-meth-
oxy substituent that for steric reasons adopts the con-
formation where the 2p-type lone pair on oxygen is nearly
perpendicular14 to the symmetry axis of the 2pz orbital
on the para carbon atom. In this geometry conjugation
between oxygen and the aromatic ring cannot take place,
and both the stabilization of the phenoxyl and the
D[ArOH] (kcal/mol) ) 97.44 - 2.93 log(k12/M-1 s-1
(14)
)
D[ArOH] (kcal/mol) ) 92.97 - 2.90 log(k12/M-1 s-1
)
(15)
It is remarkable that the two lines show the same slope

Bond Dissociation Energies of O-H Bonds
J . Org. Chem., Vol. 61, No. 26, 1996 9263
dropwise at -10 °C into a solution of trimethyl borate (30
mmol) in anhydrous ethyl ether (10 mL). When the addition
was complete the mixture was stirred for ca. 5 h at the same
temperature and then treated with a solution of 30% hydrogen
peroxide (5.8 mL) and glacial acetic acid (2.3 mL). The mixture
was kept under stirring for 24 h at the same temperature and
treated with a mixture of KOH (50 mmol), water (5 mL), and
methanol (20 mL). The product was filtered and poured into
water. This solution was washed with ethyl ether, acidified
with aqueous 10% hydrochloric acid, extracted with ethyl
ether, and dried (Na2SO4). The ethyl ether was evaporated,
and the crude product was crystallized from ethanol: yield
1
61%; mp 63 °C; H NMR (CDCl3) δ 3.77 (s, 3H, OCH3), 3.87
(s, 6H, OCH3), 5.12 (s, 1H, OH, D2O exchanged), 6.19 (s, 2H,
ArH); m/ z 184 (M+). Anal. Calcd for C9H12O4 (184.19): C,
58.69; H, 6.57. Found: C, 58.58; H, 6.50.
EP R Sp ectr a . EPR spectra were recorded on a Bruker
ESP 300 spectrometer equipped with
a Hewlett-Packard
5350B microwave frequency counter for the determination of
the g-factors, which were corrected with respect to that of
perylene radical cation in concentrated H2SO4 (g ) 2.002 58).
Photolysis was carried out by focusing the unfiltered light from
a 500-W high-pressure mercury lamp on the EPR cavity. The
temperature was controlled with a standard variable-temper-
ature accessory and was monitored before and after each run
with a copper-constantan thermocouple. Relative radical
concentrations were determined by comparing the double
integrals of at least two lines of the equilibrating phenoxyls
or, when strong line overlap was present, by comparison of
the digitized experimental spectra with computer simulated
ones. In these cases an iterative least-squares fitting proce-
dure based on the systematic application of the Monte Carlo
method was performed in order to obtain the experimental
spectral parameters of the two species including their relative
intensities.
F igu r e 3. Bond dissociation energies, BDE’s, of phenolic
compounds against the logarithm of the rate constant for their
reaction with peroxy radicals (eq 12) taken from ref 14. Empty
and filled circles indicate phenols containing methyl (O) or tert-
butyl (b) ortho substituents, respectively.
and that, for the same BDE values, the rate constants of
inhibition k12 of the o,o-di-tert-butylphenols are 30 times
lower than those of the o,o-dimethyl phenols. This
difference emphasizes the importance of steric crowding
about the hydroxylic group in decreasing the reactivity
of phenols toward peroxy radicals and therefore in
reducing their effectiveness as antioxidants.
The couples of phenols investigated to derive the series of
BDE values are the following ones: 1-1a ; 1a -2a ; 1a -3b; 1a -
3c; 1b -3b ; 1c-2a ; 1c-2b ; 1c-2c; 1c-4a ; 1c-4b ; 1c-4d ;
2a -2b; 2a -2c; 2a -3c; 2a -4a ; 2b-2c; 2b-3b; 2b-4a ; 2b-
4b; 2b-5b; 2c-4a ; 2c-4b; 2c-4d ; 3b-3c; 4a -4b; 4a -4d ;
4b-4d ; 4b-4e; 4c-4e; 4d -6a ; 4d -6b; 4e-5a ; 4e-6b.
Exp er im en ta l Section
Ma ter ia ls. Phenol (1), 4-methylphenol (1a ), 4-tert-butyl-
phenol (1b), 4-methoxyphenol (1c), 2,6-dimethylphenol (2a ),
2,6-di-tert-butylphenol (2b), 2,6-dimethoxyphenol (2c), 3,5-di-
tert-butylphenol (3b ), 3,5-dimethoxyphenol (3c), 2,4,6-tri-
methylphenol (4a ), 2,4,6-tri-tert-butylphenol (4b), 2,6-di-tert-
butyl-4-methylphenol (4d ), 2,6-di-tert-butyl-4-methoxyphenol
(4e), and R-tocopherol (6b) were commercial products used as
such unless otherwise specified. 2,3,6-Trimethyl-4-methoxy-
phenol20 (5a ) and 6-hydroxy-2,2,5,7,8-pentamethylchroman21
(HPMC) (6a ) were prepared as described in the literature.
R-Tocopherol was purified before use by column chromatog-
raphy on silica gel.13
2,3,5,6-Tetramethyl-4-methoxyphenol (5b) was obtained
from duroquinone and trimethyl phosphite by using a proce-
dure similar to that described to prepare the analogous 2,3,5,6-
tetramethyl-4-ethoxyphenol:22 yield 56%, crystallized from
aqueous ethanol: mp 112-113 °C; 1H NMR (CDCl3) δ 2.19 (s,
6H, ArCH3), 2.25 (s, ArCH3), 3.67 (s, 3H, OCH3), 4.52 (s, 1H,
OH, D2O exchanged); m/ z 180 (M+). Anal. Calcd for C11H16O2
(180.25): C, 73.30; H, 8.95. Found C, 73.23; H, 8.89.
EP R Sp ectr a l P a r a m eter s of P h en oxy Ra d ica ls. Phe-
noxyl from 1: ao(2H) 6.57 G, am(2H) 1.84 G, ap(1H) 10.07 G, g
) 2.0047; 1a : ao(2H) 6.32 G, am(2H) 1.56 G, a(Me) 11.99 G, g
) 2.0047; 1b: ao(2H) 6.24 G, am(2H) 1.96 G, a(CMe3) 0.44 G,
g ) 2.0046; 1c: ao(2H) 5.57G, am(2H) 0.70 G, a(OMe) 1.81 G,
g ) 2.0049; 2a : a(2Me) 6.75 G, am(2H) 1.94 G, ap(1H) 9.48 G,
g ) 2.0047; 2b: a(2CMe3) 0.07 G, am(2H) 1.95 G, ap(1H) 9.72
G, g ) 2.0047; 2c: a(2OMe) 1.31G, am(2H) 1.72 G, ap(1H) 8.33
G, g ) 2.0048; 3b: ao(2H) 6.51 G, a(2CMe3) ∼0 G, ap(1H) 10.34
G, g ) 2.0048; 3c: ao(2H) 5.77 G, a(2OMe) 0.40 G, ap(1H) 12.20
G, g ) 2.0046; 4a : a(2Me) 6.30 G, am(2H) 1.63 G, a(1Me) 10.96
G, g ) 2.0046; 4b: a(2CMe3) ∼0 G, am(2H) 1.71 G, a(1CMe3)
0.38 G, g ) 2.0046; 4c: a(2OMe) 1.09 G, am(2H) 0.95 G,
a(1OMe) 1.19 G, g ) 2.0050; 4d : a(2CMe3) ∼0 G, am(2H) 1.67
G, a(1Me) 11.20 G, g ) 2.0046; 4e: a(2CMe3) ∼0 G, am(2H)
0.93 G, a(OMe) 1.53 G, g ) 2.0047; 5a : a(1Me) 6.36 G, a(1Me)
4.29 G, a(1Me) 1.53 G, a(1H) 0.90 G, a(1OMe) 0.90 G, g )
2.0048; 5b: a(2Me) 6.18 G, a(2Me) 1.59 G, a(OMe) ∼0 G g )
2.0047; 6a : a(1Me) 6.03 G, a(1Me) 4.54 G, a(1Me) 0.90 G,
a(2H) 1.49 G, g ) 2.0048; 6b: a(1Me) 6.10 G, a(1Me) 4.65 G,
a(1Me) 1.02 G, a(2H) 1.60 G, g ) 2.0048.
2,4,6-Trimethoxyphenol (4c) was prepared by initial lithia-
tion of trimethoxybenzene. To a vigorously stirred solution
of 1,3,5-trimethoxybenzene (30 mmol), anhydrous TMEDA (30
mmol), and anhydrous ethyl ether (20 mL) cooled to 0 °C was
gradually added a 1.2 M solution of buthyllithium in hexane
(33 mmol) under argon; stirring was continued at the same
temperature for 1 h. The resulting mixture was then poured
Ack n ow led gm en t. Financial support from MURST,
CNR (Rome), University of Bologna (Progetto
d’Ateneo: Biomodulatori Organici), and Regione Au-
tonoma Sardegna is gratefully aknowledged.
(20) J ohn, W.; Rathmann, F. H. Chem. Ber. 1940, 73, 995.
(21) Smith, L. I.; Ungnade, H. E.; Hoehn, H. H.; Wawzonek, S. J .
Org. Chem. 1939, 4, 311.
(22) Ramirez, F.; Chen, E. H.; Deishowitz, S. J . Am. Chem. Soc.
1959, 81, 4338.
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