Synthesis and thermal stability of benzoxazine nitroxides

Article abstract of DOI:10.1021/jo2014559

A new class of stable nitroxides (aminoxyls) having a 1,4-benzoxazine structure were synthesized and the corresponding thermal stability tested. All derivatives were stable in the entire range of temperatures employed, except those having a benzyl or a te

Full text of DOI:10.1021/jo2014559

Article
pubs.acs.org/joc
Synthesis and Thermal Stability of Benzoxazine Nitroxides
Paola Astolfi and Pierluigi Stipa*
̀
S.I.M.A.U. Department - Chemistry Division, Universita Politecnica delle Marche, via Brecce Bianche, I-60131 Ancona, Italy
S
* Supporting Information
ABSTRACT: A new class of stable nitroxides (aminoxyls)
having a 1,4-benzoxazine structure were synthesized and the
corresponding thermal stability tested. All derivatives were stable
in the entire range of temperatures employed, except those having
a benzyl or a tert-butyl group at the β-position with respect to the
aminoxyl function, which underwent radical fragmentation. Such a
behavior allowed a kinetic study, carried out by means of EPR
spectroscopy, to determine the corresponding rate constants and
activation parameters (Ea). Appropriate DFT calculations were
performed for all nitroxides including also the thermally stable ones, in order to study the geometries of the fragmentation
transition States as well as to compute the corresponding bond dissociation enthalpies (BDH), useful for further modeling
purposes. The data obtained were interpreted on the basis of the relative stability of the leaving radical, according to the
corresponding Ea and BDH, whereas in the case of tert-butyl derivatives steric hindrance should play a determinant role, as
evidenced by a comparison of the geometric, kinetic, and thermodynamic parameters upon the whole series.
and nitroxides are used, the thermal stability of these radicals
and of the corresponding alkoxyamines represented a crucial
point and has to be determined.17,18
In a previous study on the radical trapping properties of
3-aryl-2H-benzo[1,4]oxazin-4-oxides,19 we noted the stability
of the nitroxide spin adducts formed by the trapping of carbon-
centered radicals, and as a consequence, we decided to prepare
a series of new benzoxazine nitroxide radicals and to study their
thermal stability.
INTRODUCTION
■
Aminoxyls (nitroxides) represent an interesting class of
persistent organic free radicals. In some cases, they are stable
and commercially available and have been widely used for years
as spin probes,1 spin labels,2 contrast agents,3 spin carriers in
molecular magnetic materials,4 and antioxidants in polymeric5 as
well as in biological systems.6 The antioxidant activity of these
compounds has mainly been attributed to their attitude to give
very fast radical−radical coupling reactions with carbon-centered
radicals.7 Their reactivity toward oxygen-centered radicals still
remains not well established,8 except for the case of aromatic
aminoxyls in which the delocalization of the free valence in an
aromatic π system is possible,9,10 as with indolinonic nitroxides.11
At the same time, electron paramagnetic resonance (EPR)
probably represents the simplest and the most useful experimental
technique to directly detect and characterize free radicals whose
persistency allows the acquisition of their EPR signals: from the full
spectral analysis hyperfine coupling constant (hfcc) values useful for
building correlations concerning the structure of the detected radical
can be obtained. However, in certain cases the correct interpretation
of these signals is not straightforward for the presence of a large
number of lines, but some improvements in density functional
theory (DFT)12 have recently led to computational methods able to
describe the properties of free radicals, including their EPR features,
with an excellent level of confidence.10,13
RESULTS AND DISCUSSION
■
3-Substituted-3-aryl-2H-benzo[1,4]oxazin-4-oxyl radicals were
prepared as summarized in Scheme 1, following a previously
described procedure:20 the appropriate Grignard reagent was
added to the nitrone and the resulting hydroxylamine was then
oxidized with lead dioxide.
The recorded EPR spectra of these nitroxides were interpreted
on the basis of hfcc typical for this kind of radicals, in which the
nitrogen three lines are mainly split by two different couples of
aromatic hydrogens of the benzoxazine moiety: H(4) and H(11)
with the larger hfcc (ca. 3 G) and H(7) and H(8) with the smaller
one (ca. 1 G). In addition, the splitting of the two nonequivalent
protons H(16) and H(17) are clearly visible, and in some
derivatives such as 1b, 1c, and 1d, further couplings with the R-
group hydrogens are present. These assignments, confirmed by
means of appropriate DFT calculations,10 are reported in Table 1
together with the EPR parameters of all synthesized nitroxides.
The EPR spectra of all synthesized aminoxyls, together with
their corresponding simulations, are collected in the Supporting
Information, and as an example, the EPR signal of 1b and its
For years, our group has been involved in the synthesis and
reactivity of indolinonic nitroxides,11,14 also used as additives in
polymers.15 In particular, these derivatives have been proposed
not only as antioxidants but also, once transformed in the
corresponding alkoxyamines, as initiators in the controlled
nitroxide-mediated polymerization (NMP) of methyl meth-
acrylate.16 However, considering the relatively high temper-
atures typical of some industrial processes in which polymers
Received: July 13, 2011
Published: October 17, 2011
© 2011 American Chemical Society
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Scheme 1. Synthesis of Derivatives 1−3(a−e) Showing the Arbitrary Atom Numbering
a
Table 1. Hyperfine Coupling Constants and g-Factors of Nitroxides 1−3(a−e)
hfcc
N−O•
H-4
H-7
H-8
H-11
H-16
H-17
N-13
H (R)
g
1a
−2.92
(−2.91)
−2.98
(−2.99)
−2.99
(−3.03)
−2.99
(−2.98)
−2.81
(−2.90)
−2.94
(−2.91)
−2.98
(−3.00)
−2.99
(−2.94)
−2.96
0.82
(1.02)
0.90
0.78
(1.01)
0.78
−2.81
(−2.85)
−2.86
(−2.93)
−2.90
(−2.95)
−2.86
(−2.95)
−2.81
(−2.84)
−2.81
(−2.83)
−2.85
(−2.92)
−2.87
(−2.86)
−2.84
0.38
(0.02)
0.27
0.73
(0.77)
0.75
10.67
(11.08)
10.84
2.00566
1b
1c
1d
1e
2a
2b
2c
2d
3b
0.48 (0.27)
0.39 (0.09)
0.50 (3H)
(0.34)
2.00558
2.00558
2.00565
2.00556
2.00570
2.00558
2.00566
2.00564
2.00558
(1.09)
0.87
(1.05)
0.72
(0.59)
0.32
(1.01)
0.71
(11.21)
10.64
(1.07)
0.87
(1.10)
0.79
(0.65)
0.32
(1.01)
0.720
(0.98)
0.75
(11.07)
10.73
0.55 (0.29)
0.15 (0.06)
0.12 (9H)
(0.08)
(1.11)
0.77
(1.06)
0.77
(0.57)
0.45
(11.17)
11.02
(1.03)
0.86
(1.02)
0.76
(0.32)
0.35
(0.75)
0.73
(11.73)
10.70
(0.01)
0.88
(1.01)
0.79
(−0.09)
0.27
(0.75)
0.79
(11.10)
10.86
0.46 (0.28)
0.39 (0.11)
0.46 (3H)
(0.93)
(1.09)
0.87
(1.06)
0.75
(0.51)
0.16
(0.99)
0.57
(11.24)
10.67
(1.05)
0.92
(1.03)
0.83
(0.11)
0.34
(0.60)
0.72
(10.60)
10.70
0.50 (0.28)
0.19 (0.09)
0.49 (0.31)
0.39 (0.12)
(−3.00)
−2.98
(−2.98)
(1.09)
0.85
(1.06)
0.75
(−2.93)
−2.86
(−2.94)
(0.48)
0.27
(0.97)
0.76
(11.20)
10.89
(1.10)
(1.06)
(0.56)
(0.99)
(11.28)
a
Hyperfine coupling constants (hfcc) in Gauss. Computed values in parentheses. All data from deaerated benzene solutions. Refer to Scheme 1 for
atom numbering.
Figure 1. (a) Experimental (black) and simulated (red) EPR spectra of nitroxide 1b; (b) spin density distribution (α−β) of nitroxide 1b computed
at the B3LYP/EPR-III level (positive values in blue and negative in green).
spin density distribution plot are shown in Figure 1, where it
can be observed the negative spin densities at H(4) and H(11)
explaining the sign of their corresponding hfcc and why smaller
hfcc values have been attributed to the other couple of aromatic
protons H(7) and H(8).
As for indolinonic nitroxides,10 this can be explained by
considering the spin delocalization which occurs in these
aminoxyls, as a consequence of the high level of coplanarity of
the condensed rings of the benzoxazine moiety, shown by the
molecular geometry of 1b reported in Figure 2, and deduced by
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Figure 2. Ball and stick representation of the optimized geometry (a) and SOMO density plot (b) (positive values in red and negative in green) of
nitroxide 1b computed at the B3LYP/EPR-III level, showing the arbitrary atom numbering.
the geometric parameters computed at the PBE0/6-31G(d) level21
reported in Table 2.
specified temperature. In fact, according to the path described
in Scheme 2, the nitroxide may undergo β-fragmentation on
Table 2. Selected Bond Angles for of Nitroxides 1−3(a−e)
Scheme 2. Thermal Fragmentation of Derivatives 1−3(a−e)
to 1−3
a
Computed at the PBE0/6-31G(d) Level
O(15)−
O(10)−
O(15)−
C(14)−
N(13)− C(5)−C(3)− N(13)−
N(13)− C(3)−C(5)−
N−O• C(9)−C(5)
C(1)
C(9)−C(6) C(9)
C(9)−C(12)
1a
1b
1c
1d
1e
2a
2b
2c
2d
3b
172.24
178.42
177.88
178.54
177.37
171.96
179.02
178.60
179.43
178.59
179.80
179.49
179.52
179.54
179.67
179.71
179.63
179.71
179.75
179.53
5.41
2.40
2.77
2.10
1.18
5.56
1.94
2.18
1.47
2.27
118.95
118.32
118.33
118.60
118.71
118.91
118.35
118.36
118.60
118.32
12.78
10.56
10.46
10.58
11.20
12.66
10.62
10.49
10.61
10.47
heating giving the diamagnetic nitrone 1−3 and the non
persistent radicals R(a−e) (typical chromatograms are reported
in the Supporting Information). Finally, these latter species
could self-react or couple with a nitroxide molecule to form the
corresponding alkoxyamine (N−OR in eq 2): both reactions
are known to be very fast7c−e and to give EPR-silent species.17
Since the EPR signal recorded during the thermal fragmenta-
tion was due exclusively to the nitroxide under investigation,
it was possible to use high modulation conditions so that
the small signal splittings merged together and the complex
EPR signal typical of these aminoxyls (see Figure 1a) was
reduced to a broad triplet of triplets, which can be easily
handled for kinetic measurements and, by repeating the experi-
ments at different temperatures to determine the activation
parameters.
a
Bond angles in degrees. Refer to Scheme 1 for atom numbering.
From the analysis of the data collected in Table 2, it can be
observed that some dihedral angle values account for the
coplanarity of the aminoxyl N−O group with respect to the
aromatic ring, and that the C(14)−N(13)−C(9) angles values
are very close to 120°, consistent with a N(13) strong sp2
character; in addition, it can be estimated that C(12) lies
outside of the benzoxazine imaginary plane defined by C(3)−
C(5)−C(9) of about 10−12°.
All these geometrical features mainly refer to the benzoxazine
moiety and do not depend on the particular R group present at
C(14). For this reason, the same considerations may be applied
to all nitroxides synthesized in the present work. Such a
molecular structure allows the extension of the single occupied
molecular orbital (SOMO), with its pronounced π character,
over the whole benzoxazine system, as clearly shown by the
distribution plot reported in Figure 2 for 1b. Moreover, in both
density plots reported in Figures 1 and 2, the different spin
distribution on the diastereotopic protons H(16)/H(17) and
H(29)/H(41) in 1b is clearly visible, thus justifying the
corresponding different hfcc values found.
A temperature range of 140−168 °C was used for such a
study. In fact, since alkoxyamines are known to be thermally
unstable and to give the parent radicals upon cleavage of the
NO−C bond,7a,b in our experimental conditions the reversible
reaction reported in eq 2 should be completely shifted to the
left, so the measured decay constants should not be affected by
this side reaction. In fact, as evidenced by the results of our
experiments collected in Table 3, only aminoxyls 1b, 1e, 2b,
and 3b showed detectable EPR signals decay at the different
temperatures used (Figure 3), while no spectral variations were
observed with time for derivatives 1−2a, 1−2c, and 1−2d, even
after 1 h of heating at the highest temperature employed in our
tests. In other words, the only nitroxides undergoing thermal
t
Similarly to the experiments done in the past with
indolinonic nitroxides,17 the thermal stability of these new
nitroxides was studied. It was carried out by means of EPR
spectroscopy following the nitroxide signal decay with time at a
fragmentation are represented by derivatives with R = Bu and
R = CH2Ph, hence releasing such “stabilized” C-centered
radicals. As a consequence, the corresponding alkoxyamines
eventually formed are known to be very unstable and should
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thermal fragmentation, it can be summarized as follows:
Table 3. Experimental Rate Constants (k), Half-Lives (t1/2),
and Activation Parameters for EPR Signal Decay in
Deaerated tert-Butylbenzene Solutions of Derivatives 1b,
1e, 2b, and 3b
a
b
c
d
b
N−O• T (°C) k × 103
t1/2 × 10−3
R2
Ea
log A
The C-centered radicals (R•) produced in this way may
undergo very fast self-reactions but, at the same time, a fast
reversible coupling with another aminoxyl molecule to yield the
corresponding alkoxyamines (N−OR)7c is also possible:
1b
147.1
156.6
162.4
164.9
142.9
147.1
151.4
156.7
161.1
167.7
142.5
148.6
154.5
161.4
167.8
140.4
152.2
157.7
164.1
0.093
0.219
0.377
0.628
0.123
0.204
0.335
0.469
0.670
1.440
0.098
0.109
0.179
0.501
1.030
0.073
0.236
0.403
0.821
7.453
3.165
1.839
1.104
5.635
3.398
2.069
1.478
1.034
0.481
7.073
6.359
3.872
1.383
0.673
9.495
2.937
1.720
0.844
0.9779
37.34
16.21
1e
0.9908
34.46
14.21
Both the above processes affect the EPR signal intensity
whose decay can be written as:
2b
3b
0.9360
0.9984
35.88
36.39
15.58
15.80
(3)
while for [R•]:
a
b
c
d
In s−1. In s. Correlation in the Arrhenius plot. In kcal/mol.
(4)
Considering that k2 is usually very high (k2 ≈ 109 M−1 s−1) while
k−1, referred to the addition of an alkyl radical to a nitrone, is
usually about 4 orders of magnitude smaller, the term k−1[N−
Ox][R•] can be neglected and eqs 3 and 4 become
decompose very quickly at the temperatures of our experiments
to give the parent radicals (eq 2). In addition, a relatively high
temperature range has been chosen to reduce experimental
errors, since the same experiments carried out at temperatures
lower than 140 °C yielded very uncertain decay traces, probably
due to the relatively small fragmentation extent. On the other
hand, at reaction temperatures higher than 180−200 °C it is
known17 that products arising from nitroxide and nitrone
oxygen atom loss are formed. Moreover, in order to further
reduce the possibility of experimental errors due to EPR line
shape changes for the different temperatures employed, the
peak-to-peak intensity variation with time was preferentially
used instead of the corresponding peak areas.
(5)
(6)
Then, by applying the steady-state approximation, this last
equation can be written as
Since the data reported in Table 3 show that only aminoxyls
having a benzyl or a tert-butyl substituent at C(14) underwent
(7)
Figure 3. Signal decay trace (peak-to-peak intensity vs time) of nitroxide 1e at 165 °C. In the inset the corresponding kinetic treatment is shown.
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and by substitution in eq 5 the aminoxyl consumption with time
can be expressed as:
(8)
From these considerations, the EPR signal decay should follow
first order kinetics, as observed experimentally, with a rate
constant being twice the actual k1.
As outlined previously, only aminoxyls with a benzyl or a
tert-butyl group at C(14) underwent thermal fragmentation,
i.e., when the leaving group is resonance stabilized or is a
tertiary radical. From these findings, it could be supposed that
the ease of aminoxyl fragmentation reflects the ease of formation
of the corresponding leaving radical (R•), which in turn depends
on its stability, thus affecting the C−C bond dissociation
enthalpy (BDH). Such a thermodynamic quantity represents an
important parameter for nitroxides modeling, since its DFT
computation within a good degree of accuracy has recently
become easier after the introduction of suitable functionals.22
In order to better understand the behavior of these nitroxides
and to find possible correlations between their structure and
their thermodynamic and kinetic properties, the C−C BDH and
activation energies (Ea) of all aminoxyls synthesized in this work,
independently from their thermal behavior, were computed using
the M06-2X23 and the MPW1K24 functionals, respectively. The
obtained values are reported in Table 4 together with the
Figure 4. Plot of gas-phase Ea vs BDH for aminoxyls 1a−e. Quantities
in kcal/mol. See text for the “1−2e corr” value explanation.
except than 1e and 2e which lie outside the correlation line,
suggesting that their BDH values result somewhat over-
estimated with respect to the corresponding (experimental)
thermal fragmentation data.
However, as stated above, the fragmentation process should
depend on the relative stability of the leaving radical R• and
hence on the BDH of the proper C−H bond in the cor-
responding hydrocarbon.25,26 For this reason the BDE values of
R−H were plotted vs the Ea and BDE of derivatives 1a−e
(Figure 5) and also in this case the data corresponding to 1e lie
out of the correlation.
Table 4. Experimental and Computed Activation Energies
(Ea), Bond Dissociation Enthalpies (BDH), Computed
C(14)−C(29) Bond Distances, And Imaginary Frequencies
(i, in cm−1) (BDH Values in Parentheses Have Been
Computed According to Ref 25)
a
Ea
b
acd
, ,
be
,
bef
, ,
bg
,
N−O•
expt
calc
BDH
61.11
r
r
i
1a
1b
1c
1d
1e
2a
2b
2c
2d
2e
3b
57.02
37.12
52.61
48.95
34.59
56.88
36.80
52.84
48.70
34.53
36.80
1.522
1.545
1.523
1.534
1.587
1.522
1.545
1.523
1.534
1.586
1.544
2.684
2.451
2.588
2.588
2.578
2.686
2.453
2.587
2.590
2.580
2.442
126.50
304.87
273.42
252.09
243.81
123.31
322.57
270.94
253.93
243.00
384.44
37.34
40.11
53.60
51.92
34.46
35.88
41.89 (36.09)
61.14
39.96
53.26
Figure 5. Plot of computed Ea (green) and BDH (red) of aminoxyls
1a−e vs the of BDE of C−H (from ref 26) and C−C (in black, from
ref 25) in the corresponding hydrocarbons. All quantities in kcal/mol.
51.74
41.70 (35.90)
39.57
36.39
In a previous paper on indolinonic nitroxides,17 similar results
were found and justified by considering a steric constraint
eventually exerted by the bulky tert-butyl group.27 The same
explanation may apply also in the present case, especially if the
relatively large C(14)−C(29) bond distances computed for 1e
and 2e (Table 4) are considered (Figure 6). In fact, when BDH,
which usually correlates with bond distances,28 is plotted against
the C(14)−C(29) bond length, a correlation was again found
for all compounds rather than 1e and 2e.
The contribution of steric effects to the hydrocarbons R−H
bond dissociation enthalpies, and the consequent choice of a
reference compound different from the commonly used CH3−
H has recently been the subject of a considerable debate.29,30
Zavitsas25 considers the “strain free” BDH and the use of the
C−C BDE in (CH3)3C−CH3 instead of the corresponding C−
H in (CH3)3C−H seems to better reproduce the effect of steric
a
b
In kcal/mol. Computed at the MPW1K/6-31+G(d,p) level.
Computed at the M062X/6-31+G(d,p)//B3LYP/6-31G(d) level.
c
d
BDH values in parentheses have been computed according to ref 25.
e
f
g
r in Å. Referred to the corresponding transition state. Modes
marked with negative sign in the corresponding frequency calculations.
C(14)−C(28) bond distances in the starting nitroxide and in the
corresponding transition state (TS); for completeness, derivative
2e is included in the table although not synthesized.
The data collected in Table 4 show that all computed Ea are
in very good agreement with experimental ones, with the lowest
values found for nitroxide 1e, followed by the benzyl derivatives
1b, 2b, and 3b (computational details in the Experimental
Section). Since BDH should follow a similar trend, a correlation
between these two quantities was checked, and it is plotted in
Figure 4 (vide infra for the explanation of the “1−2e corr” term
reported): a good correlation was found for all nitroxides
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the corresponding leaving radical. A deeper insight carried out
by means of DFT calculations evidenced that in the case of the
tert-butyl derivatives, steric hindrance should play a determinant
role, not revealed by thermodynamics but by kinetics. For these
reasons, it could be concluded that bond fragmentations could
be heavily affected by the presence of “bulky” substituents,
making the kinetic approach (i.e., Ea evaluations and/or com-
putations) more “realistic”, and hence preferable, in modeling
studies with respect to the thermodynamic one based upon
BDH comparisons. Finally, as far as thermodynamic is con-
cerned, it appears that the best correlation with experimental
Ea is found when the Gibbs free energy changes of the
fragmentation reactions are considered instead of BDH values
even in the presence of steric effects.
Figure 6. Plot of C(14)−C(29) bond distances (in Å) vs the
corresponding BDH (in kcal/mol) of aminoxyls 1a−e.
EXPERIMENTAL SECTION
■
General Methods. All chemicals were of the highest grade of
purity commercially available and used without further purification.
Melting points are uncorrected and were determined with an
electrothermal apparatus. IR spectra were recorded in the solid state
on a spectrophotometer equipped with a Spectra Tech collector for
DRIFT measurements. Mass spectra were recorded in ESI mode with
a TOF analyzer. Isotropic X-band EPR spectra were recorded on a
spectrometer system equipped with a temperature controller, a
microwave frequency counter, and an NMR gaussmeter for field
calibration; for g-factor determination the whole system was
standardized with a sample of perylene radical cation in concentrated
sulfuric acid (g = 2.00258). General EPR spectrometer settings:
microwave power 5 mW, modulation amplitude 0.1 G, field width 40
G, receiver gain 5 × 104. EPR spectral parameters for all the
synthesized nitroxides are collected in Table 1.
hindrance exerted by the t-Bu group. As a consequence, if the
BDH value of (CH3)3C−H26 is replaced with that of
(CH3)3C−CH325in the plot of Figure 5, a better correlation
is found, thus suggesting that in these fragmentations the steric
contribution represents an important factor. Moreover, since
the “steric strain” of the tert-butyl group has been estimated to
be ca 5.8 kcal/mol,25 by subtracting this quantity to the BDH
values of 1e and 2e, (marked as “1−2e corr” values) a very
good correlation (R2 = 0.9819) was found also with Ea as
shown in Figure 4. These results clearly indicate the important
effect the steric hindrance of the substituent at C(14) has,
together with the BDH values, on the thermal stability of these
aminoxyls. Finally, a good correlation was found (R2 = 0.9843)
by replacing BDHs with the corresponding Gibbs free energy
changes of the fragmentation reactions, as shown by the plot
reported in Figure 7. This latter result could be explained by
General Procedure for the Synthesis of Benzoxazine
Nitroxides. Nitrone 1−319 (1 mmol) was dissolved in dry THF,
and the proper Grignard reagent Ra−e (2 mmol) was added under a
nitrogen stream. The reaction mixture was stirred at room temperature
for 1 h; after this time, thin-layer chromatography (TLC) analyses
showed the complete disappearance of the starting nitrone. The
reaction was quenched with NH4Cl and the mixture was extracted with
Et2O (3 × 10 mL). The ethereal solution was dried with Na2SO4 and
filtered, lead dioxide was added to the solution, and the resulting
mixture was stirred for 1 h. After this time, it was filtered and the solid
was repeatedly washed with Et2O. The solvent was evaporated under
vacuum, and the residue was purified by SiO2 column chromatography
by eluting with cycloexane−ethyl acetate 9:1.
3,3-Diphenyl-2H-benzo[1,4]oxazin-4-oxyl (1a): reddish oil; yield
82%; IR (neat, cm−1) νmax = 1588, 1482, 1389, 1226; HRMS calcd for
C20H17NO2 [M + H]+ 303.1259, found 303.1258.
3-Benzyl-3-phenyl-2H-benzo[1,4]oxazin-4-oxyl (1b): orange
solid; mp 138−140 °C (absolute ethanol); yield 60%; IR (neat,
cm−1) νmax = 1585, 1482, 1389, 1229; HRMS calcd for C21H19NO2
[M + H]+ 317.1416, found 317.1402.
3-Methyl-3-phenyl-2H-benzo[1,4]oxazin-4-oxyl (1c): reddish oil;
yield 46%; IR (neat, cm−1) νmax = 1587, 1484, 1392, 1231; HRMS
calcd for C15H15NO2 [M + H]+ 241.1103, found 241.1110.
3-Ethyl-3-phenyl-2H-benzo[1,4]oxazin-4-oxyl (1d): reddish oil;
yield 80%; IR (neat, cm−1) νmax = 1586, 1483, 1392, 1229; HRMS
calcd for C16H17NO2 [M + H]+ 255.1259, found 255.1250.
3-t-Butyl-3-phenyl-2H-benzo[1,4]oxazin-4-oxyl (1e): reddish oil;
yield 80%; IR (neat, cm−1) νmax = 1588, 1483, 1389, 1226; HRMS
calcd for C18H21NO2 [M + H]+ 283.1572, found 283.1598.
Figure 7. Plot of aminoxyls 1a−e Ea vs the corresponding Gibbs free
energy changes (ΔG). Quantities in kcal/mol.
assuming that the entropic component in ΔG should in some
way include contributions from steric effects; as a consequence,
it can be deduced that, from the thermodynamic point of view,
a more “realistic” approach should consider reaction Free
Energy rather than Enthalpy changes, especially for modeling
purposes.
3-p-Chlorophenyl-3-phenyl-2H-benzo[1,4]oxazin-4-oxyl (2a): reddish
solid; mp 118−120 °C (absolute ethanol); yield 85%; IR (neat, cm−1
)
CONCLUSIONS
■
νmax = 1587, 1483, 1383, 1224; HRMS calcd for C20H16ClNO2 [M + H]+
337.0870, found 337.0897.
The newly synthesized 3-substituted-3-aryl-2H-benzo[1,4]-
oxazin-4-oxyl nitroxides resulted stable in solutions at relatively
high temperatures. Derivatives with a benzyl or a tert-butyl
group in β-position to the aminoxyl function showed a thermal
first order EPR signal decay likely due to the relative stability of
3-Benzyl-3-p-chlorophenyl-2H-benzo[1,4]oxazin-4-oxyl (2b): reddish
solid; mp 155−157 °C (absolute ethanol); yield 80%; IR (neat, cm−1
)
νmax = 1585, 1483, 1392, 1220; HRMS calcd for C21H18ClNO2 [M + H]+
351.1026, found 351.1012.
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Article
3-Methyl-3-p-chlorophenyl-2H-benzo[1,4]oxazin-4-oxyl (2c): red-
dish oil; yield 50%; IR (neat, cm−1) ν max = 1586, 1484, 1224, 1037;
HRMS calcd for C15H14ClNO2 [M + H]+ 275.0713, found
275.0705.
REFERENCES
■
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3-Ethyl-3-p-chlorophenyl-2H-benzo[1,4]oxazin-4-oxyl (2d): red
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3-Benzyl-3-p-methoxyphenyl-2H-benzo[1,4]oxazin-4-oxyl (3b): orange
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General Procedure for the Thermal Decomposition of
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Computational Details. Density functional theory12 calculations
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optimized stationary points were found to have the appropriate
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sign) corresponded to the correct reaction coordinates, also confirmed
by their visualization with appropriate programs (animations files
available as Supporting Information).
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ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental and simulated EPR spectra and optimized
geometries in Cartesian coordinates of all aminoxyls; Arrhenius
plots for thermal fragmentations of derivatives 1−3b and 1e;
optimized geometries of all fragmentation reactions Transition
structures in Cartesian coordinates and animations of the
corresponding imaginary frequencies as separate (.zip) files.
This material is available free of charge via the Internet at
http://pubs.acs.org/.
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AUTHOR INFORMATION
■
Corresponding Author
*Fax: +39 071 2204714; Tel: +39 071 2204409 E-mail: p.stipa@
univpm.it.
ACKNOWLEDGMENTS
■
MIUR (Ministero dell’Universita
̀
e della Ricerca Scientifica e
Tecnologica) is kindly acknowledged for financial support
(PRIN 2008) and Cineca Supercomputing Center for
computational resource allocation (ISCRA grant NMPALKOX,
code: HP10CLBN2R).
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