Autoxidation of hydrazones. Some new insights

Article abstract of DOI:10.1021/jo071091m

(Chemical Equation Presented) Autoxidation of hydrazones is a generally occurring reaction, leading mostly to the formation of α- azohydroperoxides. All structural kinds of hydrazones, having at least one hydrogen atom on nitrogen, are prone to autoxidation; however, there are marked differences in the rate of the reaction. Hydrazones of aliphatic ketones are 1-2 orders of magnitude more reactive than analogous derivatives of aromatic ketones. Even less reactive are the hydrazones of chalcones, which function also as efficient inhibitors of autoxidation of other hydrazones. These differences can be attributed to the reduction of the rate of the addition of oxygen to a hydrazonyl radical, which is a reversible reaction. In the case of conjugated ketones, it becomes endothermic, making this elementary step slow down and the chain termination reactions become important. Substituents influence the stability of hydrazonyl radicals and, consequently, the bond dissociation energies of the N-H bonds. In acetophenone phenylhydrazones, the substituents placed on the ring of hydrazine moiety exhibit a higher effect (Hammett ρ = -2.8) than those on the ketone moiety (ρ = -0.82), which denotes higher importance of the structure with spin density concentrated on nitrogen in delocalized hydrazonyl radical. Electronic effects of the substituents also affect the transition state for the abstraction of hydrogen atom by electrophilic peroxy radicals; NBO analysis display a negative charge transfer of about 0.4 eu from hydrazone to a peroxy radical in the transition state.

Full text of DOI:10.1021/jo071091m

Autoxidation of Hydrazones. Some New Insights
Maja Harej and Darko Dolenc*
UniVersity of Ljubljana, Faculty of Chemistry and Chemical Technology, AsˇkercˇeVa 5,
SI-1000 Ljubljana, SloVenia
darko.dolenc@fkkt.uni-lj.si
ReceiVed May 23, 2007
Autoxidation of hydrazones is a generally occurring reaction, leading mostly to the formation of
R-azohydroperoxides. All structural kinds of hydrazones, having at least one hydrogen atom on nitrogen,
are prone to autoxidation; however, there are marked differences in the rate of the reaction. Hydrazones
of aliphatic ketones are 1-2 orders of magnitude more reactive than analogous derivatives of aromatic
ketones. Even less reactive are the hydrazones of chalcones, which function also as efficient inhibitors
of autoxidation of other hydrazones. These differences can be attributed to the reduction of the rate of
the addition of oxygen to a hydrazonyl radical, which is a reversible reaction. In the case of conjugated
ketones, it becomes endothermic, making this elementary step slow down and the chain termination
reactions become important. Substituents influence the stability of hydrazonyl radicals and, consequently,
the bond dissociation energies of the N-H bonds. In acetophenone phenylhydrazones, the substituents
placed on the ring of hydrazine moiety exhibit a higher effect (Hammett F ) -2.8) than those on the
ketone moiety (F ) -0.82), which denotes higher importance of the structure with spin density concentrated
on nitrogen in delocalized hydrazonyl radical. Electronic effects of the substituents also affect the transition
state for the abstraction of hydrogen atom by electrophilic peroxy radicals; NBO analysis display a negative
charge transfer of about 0.4 eu from hydrazone to a peroxy radical in the transition state.
Introduction
Autoxidation of hydrazones is mostly neglected in these texts,
despite the fact that the reaction is interesting also from a
synthetic viewpoint. Primary products of the autoxidation, R-azo
hydroperoxides, can be used as oxygen-transfer reagents3 or
reduced to R-azo alcohols, which serve as low temperature
sources of various alkyl or aryl radicals,4 as well as in other
synthetic reactions.5 Autoxidation of hydrazones is known for
a long time and has been extensively investigated, especially
Oxidation of materials with molecular oxygen is a ubiquitous
process, important in living organisms, the environment, chemi-
cal technology, food processing, etc. Several excellent mono-
graphs and reviews address this topic, particularly the autoxi-
dation of lipids and other biologically important materials.1,2
(1) (a) Denisov, E. T.; Afanas’ev, I. B. Oxidation and Antioxidants in
Organic Chemistry and Biology; CRC Press: Boca Raton, 2005. (b)
Denisov, E. T.; Sarkisov, O. M.; Likhtenshtein, G. I. Chemical Kinetics.
Fundamentals and New DeVelopments; Elsevier: Amsterdam, 2003. (c)
Halliwell, B.; Guteridge, J. M. Free Radicals in Biology and Medicine;
Oxford University Press: Oxford, 1999. (d) Akoh, C. C., Min, D. B., Eds.
Food Lipids, 2nd ed.; Marcel Dekker: New York, 2002.
(2) Porter, N. A.; Caldwell, S. E.; Mills, K. A. Lipids 1995, 30, 277-
290. Ingold, K. U.; Bowry, V. W.; Stocker, R.; Walling, C. Proc. Natl.
Acad. Sci. U.S.A. 1993, 90, 45-49.
(3) Baumstark, A. L. Bioorg. Chem. 1986, 14, 326-343.
(4) Mathew, L.; Warkentin, J. Can. J. Chem. 1988, 66, 11-16. Chang,
Y.-M.; Profetto, R.; Warkentin, J. J. Am. Chem. Soc. 1981, 103, 7189-
7195. Jewel, D. R.; Mathew, L.; Warkentin, J. Can. J. Chem. 1987, 65,
311-315.
(5) Tezuka, T.; Sasaki, K.; Narita, N.; Fujita, M.; Ito, K.; Otsuka, T.
Tetrahedron Lett. 1989, 30, 963-966. Baumstark, A. L.; Vasquez, P. C. J.
Org. Chem. 1992, 57, 393-395.
10.1021/jo071091m CCC: $37.00 © 2007 American Chemical Society
Published on Web 08/15/2007
7214
J. Org. Chem. 2007, 72, 7214-7221

Autoxidation of Hydrazones
SCHEME 1
in the first decades of the past century. In the 1970s, the interest
in this process ceased, although many issues remained unre-
solved. Early researchers ascertained that the process takes place
spontaneously, with no need for any external stimulus, such as
light, although the irradiation may alter the rate of the reaction.6
The reaction involves an addition of one molecule of oxygen
to a hydrazone; however, the structure of the products was not
clarified at that time.7 It was found that the reactive hydrazones
contain at least one hydrogen atom on nitrogen; i.e., they must
be derived from primary hydrazines. Pausacker8 and Criegee
et al.9 established that the products are R-azohydroperoxides,
contrary to Busch and Dietz,7 who proposed the formation of
dioxetanes. The rate of the autoxidation of benzaldehyde
phenylhydrazone was found to be influenced by solvent and
substituents on either of the aromatic rings. Electron-donating
substituents enhance the rate of autoxidation, whereas the
electron-withdrawing ones diminish it. The effect is more
pronounced by substituents placed on the hydrazine moiety
rather than on aldehyde or ketone part of the hydrazone.
According to these observations, a chain reaction was postulated,
with the abstraction of hydrogen from NH group by peroxy
radicals as the rate-determining step. Nonetheless, it was not
clearly stated which hydrazones are prone to autoxidation and
which are not.
In this paper, we present a systematic study of the reactivity
of hydrazones toward molecular oxygen, with regard to their
structure. The refined mechanism of the reaction is put forward,
based on kinetic measurements and supported by quantum-
chemical calculations.
that the initiation is a bimolecular reaction between the
hydrazone and the O2 molecule, Scheme 1 can be set up.
Taking into account that with the considerable chain length
the rate of initiation equals the rate of termination, the following
expression for the reaction rate can be derived (see the
Supporting Information)
Results and Discussion
The data obtained from previous literature are quite poor and
insufficient to make any decisive conclusion about the crucial
steps in the autoxidation process. Although Pausacker measured
the reactivity of several benzaldehyde phenylhydrazones sub-
stituted on either ring, the published data are rather crude.8 There
were no measurements made on purely alkyl compounds or
alkylhydrazones of aromatic ketones and vice versa. Therefore,
we decided to measure the rate of autoxidation for a series of
compounds to obtain additional or better data.
d[RO2H]
k2k1i /2[RH]3/2[O2]1/2
V )
)
(10)
1/2
dt
2kt1
2kt2
+
2
+ 2kt3
2
{
}
K[O2]
K [O2]
where K ) k1/k-1
.
When K and/or the concentration of O2 are large, the terms
containing kt1 and kt2 in the denominator can be ignored and
the eq 10 is simplified.
Kinetics. The rates of autoxidation were measured spectro-
photometrically in heptane, saturated with oxygen under atmo-
spheric pressure (98-100 kPa). Due to the high absorptivity of
hydrazones and/or azohydroperoxides in the UV-vis, the
concentration of hydrazone suitable for measurements was in
the order of 1 × 10-4 M.10 On the other hand, the concentration
of oxygen in saturated solution in heptane at 20 °C was
estimated to 13.0 mM,11 thus enabling the pseudo first-order
kinetics to be applied, which considerably simplifies the kinetic
analysis.
d[RO2H]
ki
d[RH]
dt
) -
) k2
[RH]3/2[O2]1/2
)
dt
2k
x
t3
kobs[RH]3/2[O2]1/2 (11)
However, when this is not true, i.e., under the conditions of
low concentration of oxygen or when the equilibrium (2) is lying
on the reactant side, the omitted terms, which represent
termination reactions, become significant. These reactions may
shorten the chain length, thus reducing the overall rate of a chain
reaction.
The autoxidation of hydrazones is an autoinitiated reaction,
with the initiation step not yet clarified. With the assumption
The factor k2(ki/2kt3)1/2 is composed of rate constants of
elementary steps the values of which are more or less unknown
and can be replaced by kobs (11). Integration at constant
concentration of oxygen, i.e., under the conditions of first-order
kinetics, then gives
(6) Stobbe, H.; Nowak, R. Chem. Ber. 1913, 46, 2887-2900.
(7) Busch, M.; Dietz, W. Chem. Ber. 1914, 47, 3277-3291.
(8) Pausacker, K. H. J. Chem. Soc. 1950, 3478-3481.
(9) Criegee, R.; Lohaus, G. Chem. Ber. 1951, 84, 219-224.
(10) (a) Yao, H. C.; Resnick, P. J. Org. Chem. 1965, 30, 2832-
2834. (b) Adembri, G.; Sarti-Fantoni, P.; Belgodere, E. Tetrahedron 1966,
22, 3149-3156.
(11) Reference 1a, p 33. Golovanov, I. B.; Zhenodarova, S. M. Russ. J.
General Chem. 2005, 75, 1795-1797. Lu¨hring, P.; Schumpe, A. J. Chem.
Eng. Data 1989, 34, 250-252.
kobs
-1/2
[RH]-1/2 ) [RH]0
+
[O2]1/2t
(12)
2
where [RH]0 is the starting concentration of hydrazone.
J. Org. Chem, Vol. 72, No. 19, 2007 7215

Harej and Dolenc
namely initiation and the abstraction of hydrogen in a propaga-
tion step, have most probably some common features.13
Whatever the initiation reaction, it involves the formation of
an initial hydrazonyl radical by the abstraction of the hydrogen
atom from a hydrazone by a bi- or termolecular reaction of a
hydrazone with molecular oxygen directly or indirectly via a
redox process. Since the molecular oxygen is exceedingly
electrophilic, a substantial charge transfer is expected to occur
in the transition state. The same can be expected for the
abstraction of a hydrogen atom in the propagation step by
similarly electrophilic peroxy radicals.
The dependence of the rate on the concentration of oxygen
is demonstrated by hydrazone 8a, oxidized in heptane, saturated
with pure oxygen or with air. The measured rate of oxidation
in air is 2.2 times smaller than that in pure oxygen, yielding
essentially the same value of the kobs (Table 1).
FIGURE 1. Plot of [RH]-1/2 vs time for the autoxidation of 19 in
heptane, saturated with oxygen at 20 °C.
TABLE 1. Rate Constants of the Autoxidation of Hydrazonesa
Besides the initiation, one of the key rate-determining steps
is the abstraction of the hydrogen atom from the hydrazone (10,
11). The rate is thus expected to be inversely proportional to
the BDE N-H in the hydrazone, which is in turn linked to the
stability of the hydrazonyl radical formed. To test this hypoth-
esis, the energies of starting hydrazones, the corresponding
hydrazonyl and azoperoxy radicals were calculated for a set of
compounds (1-13, 18-22). Compounds 1a-4a were not
synthesized and measured, but are model compounds, used for
computational study only. Calculated reaction enthalpies are
presented in Table 2.
hydrazone
102kobs (M-1 s-1
)
hydrazone
102kobs (M-1 s-1
)
5a
6a
7a
1.4
76
14a
15a
16a
17a
18a
19a
20a
21a
22a
8.4
0.74
0.23
0.016
0.34
11 × 102
2.9 × 102
2.8 × 102
1.0 × 102
7.6
8a
8ab
9a
0.27
0.13
10a
11a
12a
13a
0.87
0.11
0.19
0.079
2.3 × 10-4
a Measured spectrophotometrically as a decay of the absorbance of the
starting hydrazone in heptane at 20.0 °C, saturated with O2 (98-100 kPa).
For relative errors, see the Supporting Information. b Measured in heptane
saturated with air.
When measured [RH]-1/2 were plotted against time, more or
less linear plots were obtained (Figure 1), from which kobs were
determined. The measurements were not strictly reproducible;
scattering of the rate constants up to 10% was usual, depending
on hydrazone. Therefore, an average of two to four measure-
ments is reported for each compound (Table 1). The purity of
the hydrazone is crucial; traces of hydrazines or other impurities
cause severe bending of the plot).
Enthalpies of the abstraction of hydrogen atom from hydra-
zones were calculated using one type of abstracting radical,
namely MeO2, for all substrates. In a real reaction, the
abstracting radical is a peroxy radical, derived from a particular
hydrazone (i.e., RO2). In fact, the BDE O-H in various
peroxides is hardly dependent on the type of R,14,15 and the
error thus made can be considered negligible.
It can be clearly seen from Table 1 and Figure 1 that the rate
of autoxidation is strongly influenced by the substituents at all
three positions, R1, R2, and R3 (Chart 1). Phenylhydrazones of
aliphatic ketones 6a-10a exhibit the highest reactivity, followed
by purely aliphatic hydrazone 5a, benzaldehyde alkylhydrazone
11a, and arylhydrazones of aromatic ketones 12a-22a as the
least reactive. The electronic effect of substituents, placed on
either of the aromatic rings of the hydrazone, is considerable;
however, substituents on the ring in the hydrazine moiety exhibit
a greater effect with F ) -2.3 to -2.8 (acetone substituted-
phenylhydrazones 6a-10a and acetophenone substituted-phe-
nylhydrazones 13a-17a, respectively) compared to substituents
on the ring in the ketone moiety, having F ) -0.82 (Figure
2).12 Rather high values of F indicate a substantial charge transfer
in the transition state of a rate-determining step.
The inspection of data presented in Table 2 reveals that the
energetics of the abstraction of hydrogen atom from hydrazone
is highly dependent on the number, type, and position of
substituents in the molecule of the hydrazone. The methyl group
at the hydrazine moiety (R1, 2a) lowers the energy of the
abstraction by 14 kJ/mol (compared with 1a). To the contrary,
the methyl group placed at the ketone moiety (R2, 3a) gives
rise to only 2.4 kJ/mol lowering of the BDE, and these effects
are apparently quite additive. Replacement of an alkyl group at
R1 by aryl (5a f 6a) causes additional lowering of the energy
of the abstraction by 7.5 kJ/mol, which is reflected also in the
rate of autoxidation. In a series of related acetone phenylhy-
drazones (6a-10a), the effect of the substituents placed on the
(13) Competition kinetics experiments with two hydrazones of similar
type, e.g., two differently substituted acetophenone phenylhydrazones,
The effect of substituents on the rate can be interpreted by
the influence of substituents on the energy of transition state in
a rate-determining step, i.e., particularly step (3). In a chain
reaction, there are several rate-determining steps represented
by rate constants ki, k2, and kt (eqs 10 and 11). Two of them,
1
measured by H NMR exhibit the same reactivity patterns as in absolute
kinetics. In this type of experiment, the differences in the rate of propagation
should be reflected in the product ratios. Similar reactivities under each
reaction condition point to a close relation between the initiation and
propagation steps.
(14) Luo, Y.-R. Handbook of Bond Dissociation Energies in Organic
Compounds; CRC Press: Boca Raton, 2003.
(12) The corresponding Hammett constants recalculated from from
literature rates are -1.7 for benzaldehyde substituted-phenylhydrazones and
approximately -0.7 for substituted-benzaldehyde phenylhydrazones.8
(15) Our calculations of BDE ROO-H (B3LYP/6-311G**) on several
R-azohydroperoxides yielded values which differ up to 6 kJ/mol from each
other.
7216 J. Org. Chem., Vol. 72, No. 19, 2007

Autoxidation of Hydrazones
CHART 1
TABLE 2. Calculated Reaction Enthalpies for the Abstraction of
Hydrogen from a Hydrazone (∆H2) and the Addition of Oxygen to
Hydrazonyl Radical (∆H1)a
arylhydrazine ring can be observed. Electron-donating groups
strongly reduce the N-H bond energies and the electron-
withdrawing ones enhance them; the effect is reflected in the
Hammett correlation (Figure 2) with an unusually high value
of F ) -2.3. A similar effect can also be seen in a series of
related acetophenone substituted-phenylhydrazones (13a, 18a-
21a).
b
c
∆H2
hydrazone (kJ mol-1
∆H1
∆H2
∆H1
)
(kJ mol-1
)
hydrazone (kJ mol-1
)
(kJ mol-1
)
1
2
3
4
5
6
7
8
9
26.5
12.6
24.1
-52.9
-62.9
-50.6
-62.6
-57.6
-29.6
-28.2
-29.7
-26.6
10
11
12
13
18
19
20
21
22
-10.1
-3.2
-23.8
-25.4
0.5
-10.1
-28.9
-22.6
-20.0
-18.7
-15.5
-16.5
On the other hand, substitution of an alkyl group with aryl
at the ketone moiety exhibits a smaller effect on the N-H bond
8.7
3.7
6.3
3.7
1.8
2.8
7.9
-4.4
-11.9
-26.2
-16.2
-12.9
a Calculated at the B3LYP/6-311G** level as total enthalpies at 298K.
b H(R) + H(MeO2H) - H(RH) - H(MeO2). c H(RO2) - H(R) - H(O2).
energy, and the same holds for the substituents on the arylketone
ring as well. Nevertheless, aryl rings at the either side of the
hydrazone hence stabilize the hydrazonyl radical and decrease
the BDE of the N-H bond, but only the aromatic rings at the
hydrazine moiety accelerate the autoxidation; however, those
on the ketone moiety have the opposite effect.
The answer to this anomaly lies in the rightmost column
(∆H1) of Table 2, presenting the enthalpies of the addition of
oxygen to the hydrazonyl radical. These additions are known
to be diffusion controlled and are generally exothermic in the
beginning of the table, with a gradual decrease of the energy
with increasing stabilization of the hydrazonyl radical. Introduc-
tion of an aryl ring at the position R2 (11-22) sharply changes
the sign of the enthalpy of the addition, which indicates that
the addition of oxygen has become endothermic (Figure 3). The
reason is the loss of conjugation of the hydrazonyl radical b
FIGURE 2. Hammett plots of the rates of autoxidation. 0: acetone-
substituted-phenylhydrazones, F ) -2.3 ( 0.1, R2 ) 0.89; n:
acetophenone substituted-phenylhydrazones, F ) -2.8 ( 0.1, R2 )
0.86; 4: substituted-acetophenone phenylhydrazones, F ) -0.82 (
0.1, R2 ) 0.95.
J. Org. Chem, Vol. 72, No. 19, 2007 7217

Harej and Dolenc
FIGURE 4. Transition state for the abstraction of a hydrogen atom
by methylperoxy radical from 4a, B3LYP/6-311++G**. Distances/
Å: N-H 1.191; O-H 1.275. Angle/deg: N-H-O 172.
aromatic region there is an abundance of unresolved multiplets
between 6.6 and 8.0 ppm and in the OOH region two broad
singlets appear with the integral of the major one of approx
0.35 of the expected value for pure hydroperoxide.
FIGURE 3. Energy diagram for the autoxidation of hydrazones 4a
and 12a. H (kJ/mol) calculated at the B3LYP/6-311G** (for R and
RO2), B3LYP/6-311++G**, and MPW1K/6-311++G** (for RH‚‚O2-
Me, TS and R‚‚HO2Me) levels.
Hydrazones of conjugated aromatic aldehydes or ketones, e.g.,
cinnamaldehyde or benzalacetone, are even less reactive, despite
the most exothermic abstraction of the hydrogen atom. More-
over, in mixtures with more reactive hydrazones they act as
efficient autoxidation inhibitors. Autoxidation of cinnamalde-
hyde 4-methoxyphenylhydrazone (23a) at room temperature led
SCHEME 2
1
in 6 days to the formation of a complex reaction mixture. H
with the aromatic ring upon addition of the oxygen molecule
(Scheme 2). In hydrazones of aliphatic ketones, there is no such
stabilizing conjugation of the radical b with substituents R2 or
R3 and the addition has smaller energetic effect. No appreciable
activation barrier is expected for the attachment or detachment
of an oxygen molecule, so this reaction step can be considered
as a rapidly establishing equilibrium. The addition of oxygen
molecule to delocalized C-centered radicals is, in some cases,
known to be reversible, e.g., in the autoxidation of polyunsatu-
rated fatty acids.16
NMR spectra exhibit at least five major peaks in the OMe region
and very little OOH protons (few % of theoretical, 10.7 ppm in
acetone-d6). HPLC/MS analysis revealed a multitude of com-
pounds, among which the majority exhibit a peak at the highest
m/z at 534 which corresponds to the mass of a dimer + O2 -
2. The isolation of products was not successful; however,
analysis of the spectra led us to the conclusion that the
compounds formed are most probably the coupling products of
radicals R + RO2.
The endothermicity of the addition of oxygen to the hydra-
zonyl radicals, derived from aromatic ketones and consequently,
weakness of the C-OO(H) bond in the corresponding hydro-
peroxides is most probably the principal reason for the instability
of the hydroperoxydes of this type.
The addition of an oxygen molecule to the radical b is an
association reaction and in such case it is expected that entropic
factors also play an important role. Calculated entropy change
for the addition of oxygen molecule on radical b amounts to
around -150 to -210 J mol-1 K-1, which leads at 20 °C to
approximately 44-60 kJ mol-1 on the ∆G scale.17 This means
that the addition of oxygen to hydrazonyl radical is no longer
exothermic in ∆G terms but becomes nearly thermoneutral or
slightly endothermic for hydrazones of aliphatic ketones (1-
10) and substantially endothermic for hydrazones of aromatic
ketones (11-22). The reaction (2) thus seems to be reversible
with the equilibrium lying on the left side, at least for the
hydrazones of the aromatic ketones, and it is becoming a slow
step in the process. In such case the values of terms containing
kt1 and kt2 (eq 10) increase, which results in a decrease of overall
reaction rate. Along with the growing importance of termination
reactions, one can expect an increase in the amount of the
As mentioned earlier, aromatic rings at R1 and R2 (or R3)
and the substituents placed on them, have different influences
on the BDE of the N-H bond in hydrazone. NBO Analysis of
the radical 1b demonstrates the high spin density on N1 and
N2 atoms (0.62 and 0.26, respectively), rather that on C (0.09),
Scheme 2. The weight of the resonance structure b-N seems to
be much higher than that of b-C and the substituent R1 should
have stronger effect on the energy than R2 or R3. Similarly, in
radical 12b, the spin density delocalized over aromatic ring at
R1 amounts to 0.27, which is more than twice of that on the
aromatic ring at R2 (0.13). These electronic effects are reflected
in experimentally determined reactivities (Figure 2).
•
Reaction profiles for the series RH to RO2 exhibit a relatively
1
products thereof. H NMR spectra of the reaction mixtures of
low-lying transition state (B3LYP/6-311++G**, Figures 3 and
4), surrounded by two potential wells. One corresponds to a
hydrogen-bonded complex of a molecule of hydrazone and
peroxy radical (RH‚‚‚O2Me) before the transition state while
the other represents a molecule of methyl hydroperoxide and
hydrazonyl radical (R‚‚‚HO2Me) after the TS. Low activation
enthalpy for the abstraction of hydrogen atom is consistent with
smooth chain reaction with relatively long chains. The calcula-
tion of the activation enthalpy at the MPW1K/6-311++G**
level, a method recommended for the transition states, yields
substantially higher activation enthalpies (42 and 34 kJ mol-1
autoxidation of hydrazones of aromatic ketones indeed display
complex mixtures. As an example, in a spectrum of the reaction
mixture of autoxidation of 18a in acetone d6, several peaks in
the Me as well as in the OMe region can be found. In the
(16) Tallman, K. A.; Pratt, D. A.; Porter, N. A. J. Am. Chem. Soc. 2001,
123, 11827-11828. Pratt, D. A.; Mills, J. H.; Porter, N. A. J. Am. Chem.
Soc. 2003, 125, 5801-5810.
(17) Entropies for radicals of the type R and RO2 for compounds 4 and
12 as well as O2 calculated at the UB3LYP/6-311G** level were taken
into account. Entropies are calculated for a gas-phase reaction; the effects
in solution are presumably somewhat smaller.
7218 J. Org. Chem., Vol. 72, No. 19, 2007

Autoxidation of Hydrazones
for 4 and 12, respectively).18 Such high activation barriers would
suggest slow reactions, which could not contribute to long chains
in propagation step.19 The values of activation enthalpies
computed at the B3LYP level thus seem more realistic.
The most endothermic step in a series RH f RO2 seems to
be the dissociation of the R‚‚‚HO2R complex into R and HO2R.
However, this pathway can probably be avoided by the addition
of molecular oxygen to the complex and dissociation of the new
complex afterward. Such a “bypass” would considerably reduce
the barrier going from R‚‚‚HO2R to RO2 in the case of
hydrazones of aliphatic ketones, such as 4, but has no effect in
the case of hydrazones of aromatic ketones (12).
NBO Analysis (B3LYP/6-311++G**) of the transition states
displays a significant charge transfer between hydrazone and
the methylperoxy radical in the transition state. The net charge
on methylperoxy moiety is -0.442 and -0.381 for transition
states 4 TS and 12 TS, respectively.
0.785 for TS and 0.790 for radicals b) and for this reason, the
geometries were reoptimized and total enthalpies were computed
at RODFT at 298 K as follows: H(R) ) H(U) - Etot(U) + Etot(R).
(Hydrazonyl and azoperoxy radicals have up to 10 kJ/mol lower
energies when computed at UDFT.)20 All computations were run
on Jaguar, version 6.5, Schrodinger, LLC, New York, NY, 2005.
Synthesis. Caution! R-Azohydroperoxides are potentially ex-
plosive; however, we did not experience any accidents when
working with these substances.
Hydrazones were synthesized in two ways: by Procedure 1, when
hydrazine was used in its hydrochloride form (cyclohexanone
cyclohexylhydrazone (5a),21 acetone 4-methoxyphenylhydrazone
(7a),22 acetone 4-methylphenylhydrazone (8a),23 acetone 4-chlo-
rophenylhydrazone (9a),22 benzaldehyde cyclohexylhydrazone (11a),24
acetophenone 4-methoxyphenylhydrazone (14a),25 acetophenone
4-methylphenylhydrazone (15a),26 acetophenone 4-chlorophenyl-
hydrazone (16a),27 cinnamaldehyde 4-methoxyphenylhydrazone
(23a)), or by procedure 2, when it was employed as a free base
(acetone phenylhydrazone (6a),28 acetone 4-trifluoromethylphenyl-
hydrazone (10a), benzaldehyde phenylhydrazone (12a),29 acetophe-
none phenylhydrazone (13a),30 acetophenone 4-trifluoromethylphe-
nylhydrazone (17a), 4-methoxyacetophenone phenylhydrazone
(18a),31 4-methylacetophenone phenylhydrazone (19a),32 4-chlo-
roacetophenone phenylhydrazone (20a),33 4-trifluoromethylace-
tophenone phenylhydrazone (21a), cinnamaldehyde phenylhydra-
zone (22a)).34 NMR spectra were measured on a 300 MHz
instrument and chemical shifts are reported relative to a SiMe4
reference.
Procedure 1. To a suspension of 175 mg (1.00 mmol) of
4-methoxyphenylhydrazine hydrochloride and 120 µL (1.03 mmol)
of acetophenone in 1 mL of ethanol purged with argon a solution
of 84 mg (1.00 mmol) of sodium hydrogencarbonate in 1 mL of
water was added dropwise while stirring. The reaction mixture was
stirred at room temperature under argon for 2 h. It was then cooled
to -30 °C, and the precipitate was filtered off and rinsed with water.
The crystals thus obtained were recrystallized from petroleum ether
yielding 194 mg of white crystals (14a, 81%): mp 113-114 °C
(lit.25 mp 115 °C).
Procedure 2. A 100 µL (1.016 mmol) portion of phenylhydrazine
was dissolved in 0.5 mL of ethanol and purged with argon.
4-Methylacetophenone (136 µL, 1.019 mmol) was added to the
solution, which was then left under argon at room temperature for
3 h. The mixture was cooled to -30 °C and the precipitate filtered
off and rinsed with ethanol. The crude product was recrystallized
from petroleum ether yielding 166 mg of white crystals (19a,
73%): mp 97-98 °C (lit.32 mp 97 °C).
Conclusions
Hydrazones of all structural types, having at least one
hydrogen atom on nitrogen, are susceptible to autoxidation, more
reactive being the hydrazones of aliphatic ketones and those
containing electron-donating groups, which lower the BDE of
the N-H bond as well as the activation energy for the
abstraction of hydrogen atom. This is evidenced by extensive
charge transfer in the transition state, the electron density being
shifted from hydrazone to electrophilic peroxy radical.
There are two types of hydrazones, in which the process is
very slow. The first type contains strong electron-withdrawing
groups which raise the BDE of the N-H bond the and also the
activation barrier in the abstraction of the hydrogen atom,
slowing down the rate of the abstraction of hydrogen atom (k2,
eq 3) and, consequently, the overall rate of the reaction.
The second type of slowly oxidizing compounds are hydra-
zones of aromatic ketones and conjugated vinylaromatic ketones
(chalcones), which are even less reactive. In the autoxidation
of these compounds a slow step is the addition of an oxygen
molecule to the hydrazonyl radical, causing combination reac-
tions to become important instead of the chain propagation.
Autoxidation of such compounds does not yield R-azohydro-
peroxides as products, but rather complex reaction mixtures.
Chalcone hydrazones are efficient autoxidation inhibitors for
otherwise reactive hydrazones.
(20) Henry, D. J.; Parkinson, C. J.; Mayer, P. M.; Radom, L. J. Phys.
Chem. A 2001, 105, 6750-6756.
The high degree of negative charge transfer from hydrazone
to peroxy radical in the transition state explains relatively high
values of Hammett F values of substituents on the rate of the
autoxidation.
(21) Sucrow, W.; Mentzel, C.; Slopianka, M. Chem. Ber. 1974, 107,
1318-1328.
(22) Chapman, N. B.; Clarke, K.; Hughes, H. J. Chem. Soc. 1965, 1424-
1428.
(23) Tsuge, O.; Kanemasa, S. Bull. Chem. Soc. Jpn. 1974, 47, 2676-
2681.
Experimental Part
(24) Busch, M.; Linsenmeier, K. J. Prakt. Chem. 1927, 115, 216-34.
(25) Suvorov, N. N.; Shkil’kova, V. N.; Podkhalyuzina, N. Ya. Zh. Org.
Khim. 1983, 19, 2420-2423.
Theoretical Calculations. For DFT calculations, all structures
were completely optimized at the B3LYP/6-311G** level for
molecules and radicals and at the B3LYP/6-311++G** or MPW1K/
6-311++G** for transition states and related structures. For
radicals, analytical vibrational frequencies and enthalpies were
calculated at the UDFT due to severe computation problems using
restricted wavefunctions. On the other hand, appreciable spin
contamination occurred using unrestricted DFT (<S2> was up to
(26) Sah, P. P. T.; Lei, H.-H. Science Repts. Natl. Tsing Hua UniV. [A]
1933, 2, 1-5; Chem. Abstr. 1933, 27, 4222.
(27) Sah, P. P. T.; Lei, H.-H.; Shen, T. Science Repts. Natl. Tsing Hua
UniV. [A] 1933, 2, 7-12; Chem. Abstr. 1933, 27, 4222.
(28) O’Connor, R. J. Org. Chem. 1961, 26, 4375-4380.
(29) Barnish, I. T.; Gibson, M. S. J. Chem. Soc. C 1970, 854-859.
(30) Jarikote, D. V.; Deshmukh, R. R.; Rajagopal, R.; Lahoti, R. J.;
Daniel, T.; Srinivasan, K. V. Ultrason. Sonochem. 2003, 10, 45-48.
(31) Skraup, S.; Guggenheimer, S. Chem. Ber. 1925, 58B, 2488-2500.
(32) Widman, O.; Bladin, J. A. Chem. Ber. 1886, 19, 583-589.
(33) Crowther, A. F.; Mann, F. G.; Purdie, D. J. Chem. Soc. 1943, 58-
68.
(18) Lynch, B. J.; Fast, P. L.; Harris, M.; Truhlar, D. G. J. Phys. Chem.
A 2000, 104, 4811-4815.
(19) Rate constant calculated by Eyring equation, taking ∆Hq ) 42 kJ
mol-1 and ∆Sq ) 150 J mol-1 K-1 as a typical value for a bimolecular
(34) Hearn, M. J.; Lebold, S. A.; Sinha, A.; Sy, K. J. Org. Chem. 1989,
54, 4188-4193.
reaction, is approximately 4 × 10-3 M-1 s-1
.
J. Org. Chem, Vol. 72, No. 19, 2007 7219

Harej and Dolenc
Acetone 4-trifluoromethylphenylhydrazone (10a): procedure
2; brownish white crystals (from hexane); yield 68%; mp 44-45
were unable to isolate the products in pure form due to their
instability. Some compounds crystallized from the reaction mixture
in hexane upon cooling, but decomposed into a brown oil during
the filtration. The identity of the products was assigned on the basis
1
°C; H NMR (CDCl3) δ 1.90 (s, 3H), 2.06 (s, 3H), 7.05 (s, 1H),
7.07 (d, J ) 8.5 Hz, 2H), 7.46 (d, J ) 8.5 Hz, 2H); 13C NMR
(CDCl3) δ 15.5 (CH3), 25.2 (CH3), 112.2 (CH), 121.0 (q, 2JF-C
)
of their H and 13C NMR spectra. Hydroperoxydes 5d,35 11d,24
1
32.5 Hz, C), 124.8 (q, 1JF-C ) 271 Hz, CF3), 126.5 (q, 3JF-C ) 3.8
Hz, CH), 145.7 (C), 148.2 (C); IR (KBr, cm-1) 3360 (w), 3312
(m), 2999 (w), 2948 (w), 2855 (w), 1618 (s), 1530 (s), 1410 (m),
1327 (br s), 1256 (s), 1155 (s), 1106 (br s), 1066 (s), 831 (s), 595
(m); UV (C7H16; λmax/nm, (ꢀ/L mol-1 cm-1)) 274.1 (3.52 × 104);
MS (EI, 70 eV) m/z 216 (M+, 100), 201 (13), 197 (15), 174 (18),
161 (44), 159 (43), 145 (14), 140 (29), 133 (9), 113 (10), 91 (7),
83 (8), 63 (8), 56 (53); HRMS (EI, 70 eV) calcd for C10H11F3N2
(M+) 216.087433, found 216.088020 (∆ ) 2.7 ppm). Anal. Calcd
for C10H11F3N2 (216): C, 55.53; H, 5.13; N, 12.96. Found: C,
55.35; H, 4.83; N, 12.86.
12d,10a 13d,36 16d,36 and 18d37 are known compounds.
Typical Procedure. A 40 mg (0.246 mmol) portion of acetone
4-methylphenylhydrazone was dissolved in 0.7 mL of acetone-d6
(Aldrich, 99.9% D, water content approximately 0.04%) or benzene-
d6 (Euriso-top 99.6% D, H2O < 0,02%) and purged with oxygen
at intervals. The course of reaction was followed by thin layer
chromatography (silica, 2:1 dichloromethane hexane). In 4 h, the
starting hydrazone was completely converted into 2-(4-methylphe-
nylazo)propane-2-hydroperoxide 8d.
The following hydroperoxides were not isolated; their spectra
were measured in the reaction mixtures in NMR solvents acetone-
d6 or benzene-d6. Hydroperoxides 15d, 17d, and 19d-22d were
not formed pure enough to allow their spectra to be interpreted
unabiguously.
Acetophenone 4-trifluoromethylphenylhydrazone (17a): pro-
cedure 2; white crystals (from petroleum ether); yield 61%; mp
1
105-106 °C; H NMR (CDCl3) δ 2.27 (s, 3H), 7.23 (d, J ) 8.4
2-Phenylazopropane 2-hydroperoxide (6d): 1H NMR (acetone-
d6) δ 1.44 (s, 6H), 7.51-7.53 (m, 3H), 7.74-7.77 (m, 2H), 10.81
(s, 1H); 13C NMR (acetone-d6) δ 23.0 (CH3), 104.7 (C), 124.1 (CH),
130.9 (CH), 132.8 (CH), 153.6 (C); IR (NaCl, cm-1) 3399 (br, m),
3068 (w), 2994 (m), 2942 (m), 1596 (w), 1527 (m), 1455 (s), 1361
Hz, 2H), 7.32-7.42 (m, 3H), 7.51 (s, 1H), 7.52 (d, J ) 8.4 Hz,
2H), 7.78 (dd, J ) 8.3, 1.4 Hz, 2H); 13C NMR (CDCl3) δ 12.0
(CH3), 112.7 (CH), 121.8 (q, 2JF-C ) 32.3 Hz, C), 124.7 (q, 1JF-C
) 269 Hz, CF3), 125.7 (CH), 126.6 (q, 3JF-C ) 3.8 Hz, CH), 128.40
(CH), 128.41 (CH), 138.7 (C), 143.0 (C), 147.7 (C); IR (KBr, cm-1
)
3357 (m), 3052 (w), 3040 (w), 2927 (w), 2851 (w), 1616 (s), 1528
(m), 1331 (br, s), 1264 (s), 1138 (s), 1107 (br, s), 1063 (s), 834
(s), 764 (s), 694 (m); UV (C7H16; λmax/nm, (ꢀ/L mol-1 cm-1)) 320.0
(2.11 × 104); MS (EI, 70 eV) m/z 278 (M+, 100), 259 (7), 167 (5),
159 (7), 140 (6), 118 (55), 103 (8), 77 (69); HRMS (EI, 70 eV)
calcd for C15H13F3N2 (M+) 278.103083, found 278.103650 (∆ )
2.0 ppm). Anal. Calcd for C15H13F3N2 (278): C, 64.72; H, 4.71;
N, 10.07. Found: C, 64.69; H, 4.79; N, 9.91.
(s), 1177 (s), 1147 (s), 844 (m), 765 (s), 690 (s); UV (C7H16; λmax
/
nm, (ꢀ/L mol-1 cm-1)) 265.9 (1.07 × 104), 411.0 (135).
1
2-(4-Methoxylphenylazo)propane 2-hydroperoxide (7d): H
NMR (acetone-d6) δ 1.41 (s, 6H), 3.88 (s, 3H), 7.05 (dd, J ) 6.9,
2.2 Hz, 2H), 7.76 (dd, J ) 6.9, 2.2 Hz, 2H), 10.73 (s, 1H); 13C
NMR (acetone-d6) δ 23.1 (CH3), 57.0 (CH3), 104.3 (C), 115.9 (CH),
126.0 (CH), 147.6 (C), 164.0 (C); IR (NaCl, cm-1) 3404 (br, m),
2993 (m), 2940 (m), 2840 (w), 1603 (m), 1520 (s), 1254 (s), 1177
(m), 1142 (s), 1030 (m), 838 (m); UV (C7H16; λmax/nm, (ꢀ/L mol-1
cm-1)) 303.0 (8.52 × 103), 402.5 (131).
4-Trifluoromethylacetophenone phenylhydrazone (21a): pro-
cedure 2; yellow crystals (from petroleum ether); yield 55%; mp
93-94 °C; 1H NMR (CDCl3) δ 2.23 (s, 3H), 6.91 (tt, J ) 8.0, 1.3
Hz, 1H), 7.18 (dd, J ) 8.0, 1.3 Hz, 2H), 7.30 (dt, J ) 8.0, 1.3 Hz,
2H), 7.43 (s, 1H), 7.60 (d, J ) 8.2 Hz, 2H), 7.89 (d, J ) 8.2 Hz,
2H); 13C NMR (CDCl3) δ 11.6 (CH3), 113.3 (CH), 120.7 (CH),
2-(4-Methylphenylazo)propane 2-hydroperoxide (8d): 1H
NMR (acetone-d6) δ 1.42 (s, 6H), 2.39 (s, 3H), 7.33 (dd, J ) 6.4,
1.7 Hz, 2H), 7.66 (dd, J ) 6.4, 1.7 Hz, 2H), 10.77 (s, 1H); 13C
NMR (acetone-d6) δ 22.3 (CH3), 23.1 (CH3), 104.5 (C), 124.2 (CH),
131.4 (CH), 143.2 (C), 151.6 (C); IR (NaCl, cm-1) 3399 (br, m),
2992 (m), 2940 (m), 1604 (m), 1526 (s), 1360 (s), 1179 (s), 1148
(s), 824 (s); UV (C7H16; λmax/nm, (ꢀ/L mol-1 cm-1)) 276.6 (9.25
× 103), 408.5 (136).
1
3
124.3 (q, JF-C ) 272 Hz, CF3), 125.2 (q, JF-C ) 3.8 Hz, CH),
125.6 (CH), 129.3 (CH), 129.5 (q, 2JF-C ) 32.4 Hz, C), 139.1 (C),
142.4 (C), 144.7 (C); IR (KBr, cm-1) 3357 (m), 3056 (w), 2936
(w), 1603 (s), 1505 (s), 1409 (m), 1329 (s), 1248 (s), 1154 (s),
1115 (s), 1075 (s), 1012 (m), 841 (s), 750 (s), 692 (s), 507 (m);
UV (C7H16; λmax/nm, (ꢀ/L mol-1 cm-1)) 336.0 (1.97 × 104); MS
(EI, 70 eV) m/z 278 (M+, 100), 263 (5), 259 (8), 186 (42), 145
(37), 92 (41), 69 (16), 65 (18), 57 (12); HRMS (EI, 70 eV) calcd
for C15H13F3N2 (M+) 278.103083, found 278.103820 (∆ ) 2.6
ppm). Anal. Calcd for C15H13F3N2 (278): C, 64.72; H, 4.71; N,
10.07. Found: C, 64.37; H, 4.72; N, 9.82.
2-(4-Chlorophenylazo)propane 2-hydroperoxide (9d): 1H NMR
(acetone-d6) δ 1.43 (s, 6H), 7.56 (dd, J ) 6.8, 2.2 Hz, 2H), 7.77
(dd, J ) 6.8, 2.2 Hz, 2H), 10.84 (s, 1H); 13C NMR (acetone-d6) δ
23.0 (CH3), 104.8 (C), 125.8 (CH), 131.1 (CH), 138.2 (C), 152.1
(C); IR (NaCl, cm-1) 3399 (br, m), 2993 (m), 2940 (m), 2865 (w),
1583 (m), 1524 (s), 1477 (s), 1361 (s), 1175 (s), 1147 (m), 1087
(s), 1009 (m), 836 (s); UV (C7H16; λmax/nm, (ꢀ/L mol-1 cm-1))
275.5 (9.54 × 103), 411.4 (118).
trans-3-Phenylprop-2-enal 4-methoxyphenylhydrazone (23a):
procedure 1; yellow crystals (from ethanol); yield 60%; mp 112-
2-(4-Trifluoromethylphenylazo)propane 2-hydroperoxide (10d):
1H NMR (acetone-d6) δ 1.46 (s, 6H), 7.88-7.94 (m, 4H), 10.91
(s, 1H); 13C NMR (acetone-d6) δ 23.0 (CH3), 105.2 (C), 124.7 (CH),
1
113 °C; H NMR (CDCl3) δ 3.75 (s, 3H), 6.60 (d, J ) 16.0 Hz,
1H), 6.83 (dd, J ) 6.8, 2.2 Hz, 2H), 6.95-7.03 (m, 3H), 7.20-
7.25 (m, 1H), 7.29-7.7.34 (m, 2H), 7.40-7.45 (m, 4H); 13C NMR
(CDCl3) δ 55.7 (CH3), 114.0 (CH), 114.8 (CH), 126.0 (CH), 126.4
(CH), 127.8 (CH), 128.7 (CH), 133.4 (CH), 136.8 (C), 138.4 (C),
139.2 (CH), 153.9 (C); IR (KBr, cm-1) 3298 (m), 3028 (w), 2994
(w), 2833 (m), 1616 (w), 1557 (m), 1514 (s), 1443 (m), 1242 (s),
1134 (s), 1097 (m), 1034 (m), 974 (s), 823 (s), 750 (s), 692 (s),
629 (m), 521 (m); UV (C7H16; λmax/nm, (ꢀ/L mol-1 cm-1)) 367.5
(3.06 × 104), 268.5 (1.23 × 104), 255.0 (1.24 × 104); MS (EI, 70
eV) m/z 252 (M+, 76), 237 (6), 175 (6), 130 (9), 122 (100), 115
(5), 108 (8), 103 (10), 95 (12), 77 (15); HRMS (EI, 70 eV) calcd
for C16H16N2O (M+) 252.126263, found 252.127000 (∆ ) 2.9 ppm).
Anal. Calcd for C16H16N2O (252): C, 76.15; H, 6.40; N, 11.11.
Found: C, 75.90; H, 6.49; N, 11.05.
1
3
126.0 (q, JF-C ) 272 Hz, CF3), 128.3 (q, JF-C ) 3.9 Hz, CH),
2
133.6 (q, JF-C ) 32.3 Hz, C), 155.7 (C); IR (NaCl, cm-1) 3397
(br, m), 2998 (m), 2944 (w), 1615 (m), 1414 (m), 1326 (s), 1171
(s), 1131 (s), 1066 (s), 849 (m), 658 (m); UV (C7H16; λmax/nm,
(ꢀ/L mol-1 cm-1)) 259.0 (9.87 × 103), 412.5 (162).
1-Phenylazo-1-(4-methoxyphenyl)ethyl 1-hydroperoxide (14d):
1H NMR (C6D6) δ 1.89 (s, 3H), 3.17 (s, 3H), 6.64 (dd, J ) 6.9,
2.2 Hz, 2H), 7.06 (tt, J ) 7.6, 1.5 Hz, 1H), 7.15 (dt, J ) 7.6, 1.5
Hz, 2H), 7.63 (dd, J ) 6.9, 2.2 Hz, 2H), 7.71 (dd, J ) 7.6, 1.5 Hz,
2H), 9.73 (s, 1H); 13C NMR (C6D6) δ 23.7 (CH3), 55.0 (CH3), 104.5
(C), 114.4 (CH), 125.1 (CH), 127.2 (CH), 128.5 (CH), 128.6 (CH),
(35) Hawkins, E. G. E. J. Chem. Soc. C 1971, 1474-1477.
(36) Tezuka, T.; Ando, S. Chem. Lett. 1986, 1671-1674.
(37) Baumstark, A. L.; Vasquez, P. C. J. Phys. Org. Chem. 1988, 1,
259-265.
Autoxidation. Autoxidation of the hydrazones of aliphatic
ketones led mainly to R-azohydroperoxides, while those of aromatic
carbonyl compounds gave complex mixtures. Unfortunately, we
7220 J. Org. Chem., Vol. 72, No. 19, 2007

Autoxidation of Hydrazones
140.5 (C), 145.7 (C), 162.7 (C); IR (NaCl, cm-1) 3381 (br, m),
3062 (w), 3002 (m), 2940 (w), 2839 (m), 1675 (m), 1601 (s), 1514
(s), 1447 (m), 1363 (m), 1313 (m), 1252 (s), 1106 (m), 1026 (s),
838 (s), 760 (s), 696 (s).
UV Kinetics. Rates of autoxidation of the hydrazones of aromatic
ketones were measured as a decay of absorbance of the hydrazone
UV band at 320-360 nm. In the case of aliphatic arylhydrazones,
absorption maxima of hydrazones are partially overlapped with
those of hydroperoxides (around 260 nm). In these cases, absor-
bance of product hydroperoxide (around 410 nm) was also
monitored but both measurements yielded essentially the same
result.
reaction time reached 3.5 h. Absorbance values at λmax 328 nm
were used for computations.
Acknowledgment. We thank the Slovenian Research Agency
for financial support, Drs. Bogdan Kralj and Dusˇan Zˇigon for
mass spectra, Dr. Drago Kocˇar for HPLC/MS analyses, and Dr.
Cˇrtomir Podlipnik and Profs. Bozˇo Plesnicˇar and Andrej Jamnik
for helpful discussions.
Supporting Information Available: Derivation of kinetic
expressions, rate constants of the autoxidation of hydrazones (with
errors), computed thermochemical data, and Cartesian coordinates
of the hydrazones, hydrazonyl and R-azoperoxy radicals, and some
transition states. 1H and 13C NMR spectra of compounds 10a, 17a,
21a, 23a, 6d-10d, and 14d. This material is available free of charge
via the Internet at http://pubs.acs.org.
Typical Procedure. A 0.20 mg (8.92 × 10-4 mmol) portion of
acetophenone 4-methylphenylhydrazone (15a) was dissolved in 0.5
mL of heptane (Riedel-de Haen, H2O < 0.01%) purged with argon.
A 100 µL portion of the solution was injected into a cuvette
containing 3 mL of heptane purged with oxygen, yielding the
hydrazone concentration of 5.94 × 10-5 mol L-1. A spectrum in
the range 500-230 nm was scanned at 10 min intervals until the
JO071091M
J. Org. Chem, Vol. 72, No. 19, 2007 7221