Solvent effect on the sensitized photooxygenation of cyclic and acyclic α-diimines

Article abstract of DOI:10.1016/j.tet.2006.08.091

The reaction of singlet molecular oxygen with a series of cyclic and acyclic α-diimines was studied. Time-resolved methods were used to measure total reaction rate constants and steady-state methods were used to determine chemical reaction rate constants. GC-MS was used to tentatively assign the reaction products. 5,6-Disubstituted cyclic α-diimines are singlet oxygen quenchers, but become more effective in polar solvents. A reaction mechanism involving a perepoxide intermediate or transition state leading to a hydroperoxide seems to be a key reaction path for product formation. A replacement of the phenyl substituent for a methyl substituent opens up an additional reaction involving a perepoxide-like exciplex, which increases singlet oxygen quenching of the cyclic α-diimines. The reactivity of 5,6-disubstituted cyclic α-diimines towards singlet oxygen is highly dependent on steric interactions arising from vicinal phenyl rings and from electronic effects. 1,4-Disubstituted acyclic α-diimines are, by comparison, moderate or poor singlet oxygen quenchers. Total rate constants are scarcely dependent on solvent properties, but instead correlate with the Hildebrand parameter. These results are explained in terms of a mechanism involving a dioxetane-like exciplex that gives rise to a charged intermediate leading to products.

Full text of DOI:10.1016/j.tet.2006.08.091

Tetrahedron 62 (2006) 10734–10746
Solvent effect on the sensitized photooxygenation of cyclic
and acyclic a-diimines
*
Else Lemp, Antonio L. Zanocco, German Gunther and Nancy Pizarro
€
´
´
´
ꢀ
´
Universidad de Chile, Facultad de Ciencias Quımicas y Farmaceuticas, Departamento de Quımica Organica y Fisicoquımica,
Casilla 233, Santiago-1, Santiago, Chile
Received 1 June 2006; revised 14 August 2006; accepted 18 August 2006
Available online 2 October 2006
Abstract—The reaction of singlet molecular oxygen with a series of cyclic and acyclic a-diimines was studied. Time-resolved methods were
used to measure total reaction rate constants and steady-state methods were used to determine chemical reaction rate constants. GC–MS was
used to tentatively assign the reaction products. 5,6-Disubstituted cyclic a-diimines are singlet oxygen quenchers, but become more effective
in polar solvents. A reaction mechanism involving a perepoxide intermediate or transition state leading to a hydroperoxide seems to be a key
reaction path for product formation. A replacement of the phenyl substituent for a methyl substituent opens up an additional reaction involving
a perepoxide-like exciplex, which increases singlet oxygen quenching of the cyclic a-diimines. The reactivity of 5,6-disubstituted cyclic
a-diimines towards singlet oxygen is highly dependent on steric interactions arising from vicinal phenyl rings and from electronic effects.
1,4-Disubstituted acyclic a-diimines are, by comparison, moderate or poor singlet oxygen quenchers. Total rate constants are scarcely depen-
dent on solvent properties, but instead correlate with the Hildebrand parameter. These results are explained in terms of a mechanism involving
a dioxetane-like exciplex that gives rise to a charged intermediate leading to products.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
obtain. Values of kQ and kR can be solvent dependent, where
solvent may modify each to a similar extent, thus keeping kR/
kT constant. Such a similar behaviour can then be ascribed to
an analogous mechanism and/or a common transition state.
However, differences in the solvent effect between kQ and
kR would suggest dissimilar transition states for each pro-
cess. For example, a reaction containing different intermedi-
ates or different pathways may still follow from a common
intermediate. Thus, the analysis of solvent effect on kT
and/or kR provides valuable information regarding the nature
of the reaction process. Many singlet oxygen reaction rate
constants measured before 1999 have been compiled by
Wilkinson et al.1 Solvent effects on singlet oxygen reactions
have been reviewed,2–6 where rate constant differences
have been correlated with solvent dielectric constants,7–9
solvent hydrogen bonding (with the target molecule),10
and/or hydrophobic interactions.11 In the last decade, linear
solvation energy relationships (LSER) and theoretical linear
solvation energy relationships (TLSER) have been em-
ployed to interpret singlet oxygen reaction mechanisms with
amine,5,12–16 polycyclic aromatic compounds,11 furan,17
alkaloids5,18,19 and biologically active (polyfunctional) com-
pounds.14,17,18,20,21 Such LSER treatments allow a quan-
titative evaluation of solvent effect in terms of different
descriptors. The relative contribution of each descriptor in-
cluded in the correlation equation depends on the substrate.
Common features are observed for compounds belonging
to the same family reacting through the same mechanism.
The interaction of singlet oxygen (O2(1Dg)) with a target
molecule (Q) involves physical (deactivation) and/or chem-
ical (reactive) processes. This process can be represented in
Eqs. 1–3
kd
1O2
O2
ð1Þ
ð2Þ
kQ
1O2 þ Q
Q þ O2
kR
1O2 þ Q
products
ð3Þ
where kd is the solvent dependent decay rate of singlet oxy-
gen that determines its unperturbed lifetime (to¼1/kd), kQ
corresponds to a second-order rate constant of physical deac-
tivation and kR is the second-order rate constant of the reac-
tive pathway. Measurement of the lifetime of singlet oxygen
at different concentrations of Q permits one to obtain a kT
value, where kT¼kQ+kR. Evaluation of kR requires the mea-
surement of quantum yields of oxygen consumption and/or
product formation, where these values can be difficult to
* Corresponding author. Tel.: +56 2 9782877; fax: +56 2 9782868; e-mail:
elemp@ciq.uchile.cl
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.08.091

E. Lemp et al. / Tetrahedron 62 (2006) 10734–10746
10735
The determination of a model compound correlation equa-
N
tion permits to calibrate and validate the linear free energy
relationship in a given solvent set, giving a basis for predic-
tions to the behaviour in other solvents. The formalism may
be used to determine the main reaction site in polyfunctional
compounds, to detect changes in the reaction mechanism
with solvent properties, and to evaluate the relative contribu-
tion of tautomers in equilibrium to the total reaction rate.
Also, the analysis could be extended to singlet oxygen
reactivity in microheterogeneous systems to predict relative
rate constants in such systems. However, when using
this formalism, several limitations should be considered.
First, this type of multilinear correlation is based on the
assumption that the various descriptors are orthogonal, i.e.,
for a given parameter there is no cross-correlation with the
other. Second, the barely reproducible rate constant values
reported by different laboratories must be carefully stated
to improve data reproducibility, which depends on various
experimental critical points—e.g., sensitizer stability and
reactivity, solvent purity, time of reaction and substrate
consumption fraction in steady-state experiments, laser
power and number of accumulated shots in time-resolved
techniques.
N
CH3
CH3
N
N
6
N
5
CH3
N
7
OMe
OMe
OMe
N
N
N
CH3
N
8
9
N
OMe
H3C
N
H3C
MeO
N
CH3
CH3
N
10
11
Figure 1. Structures of cyclic a-diimines: 5,6-dimethyl-2,3-dihydropyra-
zine (5), 5-methyl-6-phenyl-2,3-dihydropyrazine (6), 5,6-diphenyl-2,3-
dihydropyrazine (7), 5-methyl-6-(p-methoxyphenyl)-2,3-dihydropyrazine
(8), 5,6-bis(p-methoxyphenyl)-2,3-dihydropyrazine (9), and acyclic a-di-
imines: 1,4-diaza-1,4-diphenyl-2,3-dimethyl-1,3-butadiene (10), 1,4-diaza-
1,4-bis(p-methoxyphenyl)-2,3-dimethyl-1,3-butadiene (11).
A large number of studies have focused on reactions of sin-
glet oxygen with molecules containing C]C double bonds.
On the contrary, little data is available on reactions of singlet
oxygen with molecules containing C]N double bonds.22–26
A product distribution may depend on temperature and sub-
stituents in reactions of O2(1Dg) with imino compounds and
may involve several intermediates (Scheme 1), i.e., dioxaze-
tidines (1) from [2+2] concerted cycloaddition to the
carbon–nitrogen double bond;23,24 peroxide ions (2) from
electrophilic attack on iminic carbon23 and hydroperoxides
(4) from rearrangement of pernitrones (3) in reactions with
substituted 2,3-dihydropyrazines.27 The involvement of
a pernitrone intermediate (3) may arise by the interaction
of 1O2 with the imine nitrogen lone pair.
reaction rate constants, kR, for 5,6-dimethyl-2,3-dihydro-
pyrazine (5) were very close to kT in polar solvents such as
propylencarbonate, whereas the contribution of the chemical
channel to the total reaction is very low for methyl and
phenyl derivatives. Analysis of solvent effect on kT for the
dimethyl derivatives using the semiempirical solvatochro-
mic equation (LSER) of Taft, Kamlet et al.,29,30 reveals a
dependence on the solvent microscopic parameters a and
p*. When the phenyl group is replaced with a methyl group,
the dihydropyrazine ring reactivity increases towards singlet
oxygen and modifies the dependence of kT on solvent para-
meters. The importance with the Hildebrand parameter is
apparent.
Previous studies do not permit one to conclude whether the
reaction of singlet oxygen and the imino group is similar to
homologous alkenes or whether it departs significantly from
this chemistry due to the presence of the nitrogen atom. In
previous works,28 we reported the total rate constant values,
kT, and the chemical reaction rate constant values, kR, for
the reactions between two 5,6-disubstituted-2,3-dihydropyr-
azines and singlet oxygen in various solvents. Chemical
In the present work, we study reactions of singlet oxygen
with cyclic and acyclic a-diimines that possess different sub-
stituents on the iminic carbon (Fig. 1). Our aim is to under-
stand the reaction mechanism based on product distributions
and kinetics, which includes measurements of rate constants
for chemical and physical reaction channels in several sol-
vents. Solvent effects are analyzed in terms of linear solva-
tion energy relationships (LSER).29–31 LSER relations are
N
N
CH3
CH3
R
C
N
NHR''
N
CH3
CH2
N
CH3
CH3
R
R'
O2 (1
)
C
O
N NR''
g
N+
O
R'
N
R
O
OOH
C
N NH
O
R'
4
3
2
R
C
N
O
NH
R'
O
1
Scheme 1.

10736
E. Lemp et al. / Tetrahedron 62 (2006) 10734–10746
of great value in interpreting mechanisms of singlet oxygen
reactions since they may permit a quantitative explanation of
solvent effects.5
consumption rate of 9,10-dimethylanthracene in the absence
and the presence of dihydropyrazine derivatives.18 Thus,
possible rapid chemical changes of samples during illumina-
tion or interference on O2(1Dg) luminescence with the
scattered laser light and the tail end of the sensitizer fluores-
cence33 can be dismissed.
2. Results
2.1. Total reaction of singlet oxygen with cyclic
a-diimines
A solvent dependence is observed in the total quenching rate
constants for all reactions of 5,6-disubstituted-2,3-dihydro-
pyrazines with singlet oxygen (Table 1). The largest effect
was found for 5, for which kT increases by more than 2 orders
of magnitude when the solvent was changed from hexa-
fluoro-2-propanol to N,N-dimethylacetamide. Similar trends
were observed for 6, 7, 8 and 9. The total rate constant value
increases by more than 1 order of magnitude when the sol-
vent is changed from protic to non-protic solvents, such as
trifluoroethanol vs N,N-dimethylformamide. In addition, in
all solvents the total rate constant for 6 was considerably
larger than those for the other cyclic a-diimines. Dihydro-
pyrazines exhibit similar results to those reported for di-
enes.1 Thus, the reactivity of the compounds towards
singlet oxygen depends both on dihydropyrazine structure
as well as solvent properties.
The total quenching rate constant (physical and chemical),
kT, for reaction of O2(1Dg) with the 5,6-disubstituted-2,3-di-
hydropyrazines (Fig. 1) in several solvents was obtained
from the first-order decay of O2(1Dg) in the absence (tꢀo 1
)
and the presence of dihydropyrazine (tꢀ1) according to
Eq. 4.
Â
Ã
tꢀ1 ¼ tꢀo 1 þ kT dihydropyrazine
ð4Þ
Linear plots of tꢀ1 vs [dihydropyrazine] were obtained for
all solvents employed (Fig. 2). Intercepts of these plots
match closely with those reported20 and measured (in a large
number of experiments from our laboratory) for singlet
oxygen lifetimes in the identical solvents. Values of kT
calculated from slopes of these plots are given in Table 1.
The kT values were independent of the laser pulse energy
(between 2 and 5 mJ) allowing us to disregard secondary
processes involving O2(1Dg). Singlet oxygen decays after
dye laser excitation at 532 nm, with Rose Bengal as sensi-
tizer in acetone, in the absence and the presence of 5,6-di-
methyl-2,3-dihydropyrazine (5) are shown in the inset of
Figure 2. As can be observed, both traces have nearly the
same amplitude, indicating that the excited states of the sen-
sitizer were not deactivated by the addition of 5 at the
concentrations employed to quench O2(1Dg). The same be-
haviour was observed with TPP—the sensitizer employed
in most solvents—in the presence of the different dihydro-
pyrazines studied. The same kT values were obtained for
some solvents (data not shown) either by using competitive
steady-state methods, such as the inhibition of the autoxida-
tion rate of rubrene (lmax¼520 nm)32 or by following the
However, solvent effects observed here are larger than those
for dienes2 and cannot be associated merely with changes in
macroscopic solvent properties due to the existence of spe-
cific solute–solvent interactions.2,5,28 Thus, a deeper ration-
alization of solvent effects and interactions of singlet oxygen
with dihydropyrazines can be obtained from the analysis
of the quenching rate constant dependence on microscopic
solvent parameters. The semiempirical solvatochromic
equation (LSER) of Taft, Kamlet et al.29–31 (Eq. 5) was
employed.
2
log k ¼ log ko þ spꢁ þ dd þ aa þ bb þ hrH
ð5Þ
In Eq. 5, p* accounts for polarizability and dipolarity of
solvent,31,34 d is a correction term for polarizability, a corre-
sponds to the hydrogen bond donor solvent ability, b indi-
cates solvent capability as a hydrogen bond acceptor, and
rH is the Hildebrand parameter, a measure of disruption of
solvent–solvent interactions in creating a cavity.35 The con-
stant term log ko in Eq. 5 arises from the method of multiple
linear regression and does not have a clear-cut physical
meaning. For correlation equations independent of the cavity
term, the constant term log ko is equal to log k in solvents such
as alkanes, in which all the other parameters are near to zero.
7
6
5
The coefficients in the LSER equation (Eq. 5), s, d, a, b and
h, are obtained by a multilinear correlation analysis on kT de-
pendence with solvent parameters (Table 2). This analysis is
supported on purely statistical criteria. Sample size N, prod-
uct correlation coefficient R, standard deviation SD, and the
Fisher index of equation reliability F, indicate the quality of
the overall correlation equation. The reliability of each term
is indicated by t-statistic t-stat, and the variance inflation
factor VIF. Suitable quality is indicated by large N, F, and
t-stat values; small SD values; and R and VIF close to one.36
1,2
4
0,8
0,4
3
0,0
0
50
100
150
2
time/ s
0
10
20
[MPD]/mM
30
40
Figure 2. Stern–Volmer plot for deactivation of singlet oxygen by DMD
in acetone. Inset (a) Singlet oxygen phosphorescence decay at 1270 nm,
following dye laser excitation at 532 nm, with Rose Bengal as sensitizer
in acetone. (b) as (a), but with 13.6 mM DMD.
Results in Table 2 show that not all descriptors are statisti-
cally reliable. Descriptor coefficients accepted in the corre-
lation equation were those having a significance level ꢂ0.95.

E. Lemp et al. / Tetrahedron 62 (2006) 10734–10746
Table 1. Values of kT for reactions of cyclic a-diimines with O2(1Dg) in different solvents
10737
Solvent
kT/105 Mꢀ1 sꢀ1
5
6
7
8
9
Hexafluoro-2-propanol
Trifluoroethanol
Methanol
Ethanol
n-Propanol
n-Butanol
n-Pentanol
Benzyl alcohol
n-Hexane
n-Heptane
Chloroform
Benzene
Anisole
Diethyl ether
Benzonitrile
Methylene chloride
Acetonitrile
Tetrahydrofuran
Ethyl acetate
Acetone
0.26ꢃ0.01
1.52ꢃ0.16
5.23ꢃ0.22
3.69ꢃ0.19
8.60ꢃ0.38
4.94ꢃ0.22
5.44ꢃ0.19
4.48ꢃ0.21
3.60ꢃ0.17
4.31ꢃ0.18
3.16ꢃ0.13
5.34ꢃ0.21
6.01ꢃ0.33
6.08ꢃ0.31
6.25ꢃ0.41
7.36ꢃ0.31
9.87ꢃ0.41
12.9ꢃ0.48
13.6ꢃ0.58
13.7ꢃ0.43
14.6ꢃ0.55
19.3ꢃ0.72
20.3ꢃ0.89
56.8ꢃ2.34
58.3ꢃ2.61
—
0.28ꢃ0.01
1.75ꢃ0.08
10.6ꢃ0.50
8.98ꢃ0.46
7.20ꢃ0.32
—
—
0.44ꢃ0.02
0.87ꢃ0.04
1.67ꢃ0.07
2.34ꢃ0.11
2.83ꢃ0.12
3.36ꢃ0.18
3.06ꢃ0.17
3.11ꢃ0.17
—
5.74ꢃ0.25
3.54ꢃ0.18
20.1ꢃ0.99
13.0ꢃ0.66
12.7ꢃ0.64
19.1ꢃ0.96
—
12.7ꢃ0.67
10.7ꢃ0.56
12.1ꢃ0.55
—
18.5ꢃ0.89
24.5ꢃ1.29
16.8ꢃ0.70
24.8ꢃ1.17
12.8ꢃ0.59
23.1ꢃ1.11
25.5ꢃ1.15
32.1ꢃ1.70
31.1ꢃ1.59
42.7ꢃ2.01
46.5ꢃ2.22
45.9ꢃ2.30
—
26.4ꢃ1.15
22.1ꢃ0.99
25.5ꢃ1.09
—
—
—
7.56ꢃ0.35
23.3ꢃ0.09
—
—
—
28.9ꢃ1.15
—
12.0ꢃ0.06
49.5ꢃ1.98
63.0ꢃ2.29
37.7ꢃ1.69
41.9ꢃ1.65
37.1ꢃ1.29
67.3ꢃ3.02
50.6ꢃ2.85
51.6ꢃ2.12
60.4ꢃ2.63
60.8ꢃ3.00
101.0ꢃ4.19
68.1ꢃ3.27
159.0ꢃ4.38
—
3.56ꢃ0.21
5.66ꢃ0.29
11.4ꢃ0.33
9.32ꢃ0.41
8.35ꢃ0.31
4.56ꢃ0.24
7.99ꢃ0.32
11.7ꢃ0.51
11.1ꢃ0.48
11.2ꢃ0.31
11.7ꢃ0.37
23.6ꢃ1.08
18.4ꢃ0.90
12.6ꢃ0.65
—
1.67ꢃ0.08
2.78ꢃ0.15
3.36ꢃ0.17
4.81ꢃ0.27
2.97ꢃ0.18
2.50ꢃ0.15
2.83ꢃ0.14
4.63ꢃ0.28
3.53ꢃ0.20
3.95ꢃ0.19
2.99ꢃ0.17
5.93ꢃ0.31
4.70ꢃ0.24
3.03ꢃ0.17
—
Dioxane
N,N-Dimethylformamide
Propylencarbonate
Tributyl phosphate
N,N-dimethylacetamide
—
Table 2. LSER correlation equations for the reaction of singlet oxygen with cyclic a-diimines
log k¼log ko+sp*+dd+aa+bb+hrH
2
5
log ko
5.577
0.081
68.802
<0.0001
—
s
D
a
b
h
Coeff.
ꢃ
0.629
0.140
4.500
0.0002
1.536
ꢀ0.406
0.102
ꢀ3.964
0.0008
1.808
ꢀ0.602
0.439
0.125
3.507
0.0024
1.572
—
—
—
—
—
0.054
t-Stat.
P(2-tail)
VIF
ꢀ11.053
<0.0001
1.006
N¼24, R¼0.956, SD¼0.144, F¼50.029
6
log ko
6.395
0.056
114.69
<0.0001
—
s
D
a
b
h
Coeff.
ꢃ
—
—
—
—
—
—
—
—
—
—
ꢀ0.692
0.203
0.084
2.430
0.0291
1.379
0.003
0.001
4.561
0.0004
2.088
0.050
t-Stat.
P(2-tail)
VIF
ꢀ13.855
<0.0001
1.613
N¼18, R¼0.970, SD¼0.075, F¼74.475
7
log ko
5.426
0.072
75.320
<0.0001
—
s
D
a
b
h
Coeff.
ꢃ
—
—
—
—
—
—
—
—
—
—
ꢀ0.596
0.595
0.112
5.299
<0.0001
1.449
0.004
0.001
4.855
0.0002
1.587
0.046
t-Stat.
P(2-tail)
VIF
ꢀ12.853
<0.0001
1.300
N¼19, R¼0.976, SD¼0.101, F¼99.432
8
log ko
5.959
0.065
92.242
<0.0001
—
s
D
a
b
h
Coeff.
ꢃ
—
—
—
—
—
—
—
—
—
—
ꢀ0.589
0.376
0.093
4.048
0.0011
1.402
0.003
0.001
4.198
0.0008
2.036
0.060
t-Stat.
P(2-tail)
VIF
ꢀ9.873
<0.0001
1.585
N¼19, R¼0.943, SD¼0.094, F¼40.038
9
log ko
5.381
0.034
159.483
<0.0001
—
s
D
a
b
h
Coeff.
ꢃ
—
—
—
—
—
—
—
—
—
—
ꢀ0.363
0.469
0.060
7.803
<0.0001
1.000
—
—
—
—
—
0.029
t-Stat.
P(2-tail)
VIF
ꢀ12.458
<0.0001
1.000
N¼21, R¼0.961, SD¼0.074, F¼109.904

10738
E. Lemp et al. / Tetrahedron 62 (2006) 10734–10746
For this reason rH was not included in LSER correlation for
5. Similarly, equations for 6, 7, 8 and 9 were independent of
p* parameter. According to the LSER coefficients in Table
2, kT values for 5 increase in solvents with larger capacity
to stabilize charges and dipoles and decrease in strong
HBD solvents.
spectrometer in both the positive chemical ionization
(CI+) as well as the electron impact (EI+) modes. A chro-
matogram of 6 shows only three major peaks. Unreacted 6
is the main one. The CI+ and EI+ mass spectra correspond-
ing to peaks with largest retention times indicate that
1-isocyano-2-(benzoylamino)ethane (6a) and 1-isocyano-
4-phenyl-4-carboxaldehyde-3-aza-3-butene (6b) are the
probable main products of photooxidation of 6 (Scheme
2). Additionally, in separate experiments in benzene, we
confirmed the formation of formaldehyde (12) as one of
the photooxidation products by comparison with a chromato-
gram obtained for formaldehyde in benzene. For 5 we found
formaldehyde (12), 1-isocyano-2-(acylamino)ethane (5a)
and 1-isocyano-4-carboxaldehyde-3-aza-3-pentene (5b)
and for 8 we detected formaldehyde (12), 1-isocyano-2-(4-
methoxybenzoylamino)ethane (8a) and 1-isocyano-4-(4-
methoxyphenyl)-4-carboxaldehyde-3-aza-3-butene (8b) as
the probable main reaction products (Scheme 2). These
results show that the photooxidation of 5, 6 and 8 follows
the same reaction path.
Furthermore, for other compounds under study, the rate con-
stants increase in HBA solvents with high cohesive energy
and decrease in strong HBD solvents, although rate constant
for 9 does not depend on the Hildebrand parameter.
2.2. Chemical reaction of O2(1Dg) with
dihydropyrazines
Irradiation of aerated solutions of 5, 6 and 8 in the presence
of TPP or RB, at the wavelength where only the sensitizer
absorbs, decreases the concentration of these dihydropyra-
zine compounds. Plots of ln [dihydropyrazine] versus t indi-
cate that the photooxidation reaction follows a first-order
kinetics, Eq. 6.
R
R
N
R
N C
+
NH C
+
h
r ¼ kR½1O2ꢄ½dihydropyrazineꢄ ¼ kobs½dihydropyrazineꢄ ð6Þ
O
CHO
C-
+
HCHO +
acetonitrile, TPP
C-
N
CH3
N
N
A compound of known reactivity towards singlet oxygen,
such as dimethylanthracene (DMA) has been employed as
actinometer to evaluate the steady-state concentration of
O2(1Dg). The reactive rate constants for dihydropyrazines
can be evaluated from Eq. 7:
Z
X
12
Y
R
X
5
6
8
Y
Z
CH3
5a 5b
6a 6b
8a 8b
CH3-O-
dihydropyrazine
obs
k
Scheme 2.
kRdihydropyrazine ¼ kRactinometer
ð7Þ
actinometer
obs
k
2.3. Total reaction of singlet oxygen with acyclic
a-diimines
We previously reported the rate constant values, kR, for
chemical quenching of O2(1Dg) by 5 and 6, in various sol-
vents (for compound 5, kR (n-hexane)¼0.06ꢅ105 Mꢀ1 sꢀ1
;
The total quenching rate constant (physical and chemical),
kT, for reaction of O2(1Dg) with acyclic a-diimines (Fig. 1)
in several solvents was obtained from the first-order decay
of singlet oxygen luminescence as described for cyclic
compounds (Eq. 6). The values of kT obtained from these
experiments are summarized in Table 3.
kR (propylencarbonate)¼21.0ꢅ105 Mꢀ1 sꢀ1; for compound
6, kR (benzene)¼2.18ꢅ105 Mꢀ1 sꢀ1; kR (propylencarbonate)¼
1.53ꢅ105 Mꢀ1 sꢀ1).28 For compound 8, we found values
of kR very close to those obtained for MPD (kR (benzene)¼
1.96ꢅ105 Mꢀ1 sꢀ1). For 7 and 9, we found neither substrate
consumption nor product formation when monitoring the
photosensitized oxidation of these compounds up to 60 h
of irradiation—in ethanol or propylencarbonate as sol-
vent—according to gas chromatography with NPD detec-
tion. For 9 in acetonitrile as solvent and TPP as sensitizer,
we determined a consumption of 4% after 60 h irradia-
tion. With a careful control of experimental conditions
(photon flux, temperature and cell geometry) we measured
a singlet oxygen steady-state concentration to be equal to
(1.2ꢃ0.3)ꢅ10ꢀ10 M with DMA as actinometer. This result
The reactivity of acyclic a-diimines (10 and 11) towards sin-
glet oxygen is diminished compared to the cyclic homolo-
gous. The total quenching rate constants are 1–2 orders of
magnitude smaller compared to those for 5,6-disubstituted-
2,3-dihydropyrazines (Table 3).
1,4-Diaza-1,4-bis(p-methoxyphenyl)-2,3-dimethyl-1,3-buta-
diene (11) is the more reactive compared to 1,4-diaza-1,4-
diphenyl-2,3-dimethyl-1,3-butadiene (10) and is strongly
solvent dependent with respect to the total rate constant. For
11, kT increases by more than 1 order of magnitude when the
solvent is changed from trifluoroethanol (kT¼1.37ꢃ0.07ꢅ
implies that kR values for 7 and 9 would be ꢆ103 Mꢀ1 sꢀ1
,
and the chemical quenching of singlet oxygen is negligible.
Because of the low substrate concentrations employed and
the low conversion yields, no attempts were made to isolate
reaction products for spectroscopic characterization. Tenta-
tive evidence for product distribution was obtained by
GC–MS analysis. GC–MS analyses were carried out after
irradiation for 6 h, where 0.001 M substrate (w30 to 40%
conversion) was used in acetonitrile solution with TPP
as sensitizer. Chromatograms were obtained operating the
105 Mꢀ1 sꢀ1
)
to N,N-dimethylformamide (kT¼15.2ꢃ
0.80ꢅ105 Mꢀ1 sꢀ1). The acyclic a-diimine 10 shows a
smaller reactivity with total rate constant values in the order
of 104 Mꢀ1 sꢀ1 and sparingly solvent dependent. In Table 4
the equation coefficients obtained from the LSER analysis
for 11 are included. Our results show that kT increases in sol-
vents with a larger capacity to stabilize charges and dipoles,
high cohesive energy and decrease in strong HBD solvents.

E. Lemp et al. / Tetrahedron 62 (2006) 10734–10746
10739
Table 3. Values of kT for reactions of acyclic a-diimines with O2(1Dg) in
different solvents
Table 5. Chemical reaction rate constants, kR, for reactions of 1,4-diaza-1,4-
diphenyl-2,3-dimethyl-1,3-butadiene (10) and 1,4-diaza-1,4-bis(p-methoxy-
phenyl)-2,3-dimethyl-1,3-butadiene (11) with O2(1Dg) in different solvents
Solvent
kT/105 Mꢀ1 sꢀ1
Solvent
kR/105 Mꢀ1 sꢀ1
10
11
10
0.035ꢃ0.002
11
Hexafluoro-2-propanol
Trifluoroethanol
Ethanol
n-Propanol
n-Butanol
n-Pentanol
Acetonitrile
Acetone
Ethyl acetate
N,N-Dimethylformamide
N,N-Dimethylacetamide
Benzene
n-Hexane
n-Heptane
Chloroform
Dioxane
Propylencarbonate
Benzonitrile
Tetrahydrofuran
Anisole
0.14ꢃ0.01
0.26ꢃ0.01
0.49ꢃ0.02
0.41ꢃ0.02
0.48ꢃ0.02
0.35ꢃ0.02
0.16ꢃ0.01
0.12ꢃ0.01
0.12ꢃ0.01
0.35ꢃ0.02
0.34ꢃ0.02
0.37ꢃ0.02
0.17ꢃ0.01
0.14ꢃ0.01
0.42ꢃ0.02
0.24ꢃ0.01
0.29ꢃ0.01
0.16ꢃ0.01
0.15ꢃ0.01
0.28ꢃ0.01
0.21ꢃ0.01
—
1.37ꢃ0.07
3.39ꢃ0.15
1.69ꢃ0.07
2.40ꢃ0.13
2.15ꢃ0.12
10.1ꢃ0.49
8.05ꢃ0.38
4.71ꢃ0.25
15.2ꢃ0.80
12.5ꢃ0.65
6.48ꢃ0.35
1.81ꢃ0.10
2.19ꢃ0.11
3.70ꢃ0.17
6.25ꢃ0.32
14.6ꢃ0.70
8.55ꢃ0.44
4.51ꢃ0.20
6.05ꢃ0.31
2.73ꢃ0.11
Benzene
Propylencarbonate
0.216ꢃ0.012
2.120ꢃ0.090
0.0686ꢃ0.038
that there is a small contribution (in the order of 20%) of
the chemical reaction to the total singlet oxygen quenching.
The physical quenching is the major deactivation process.
Similar to the dihydropyrazines (low substrate concentra-
tion, low conversion yields), we did not attempt to isolate
reaction products for spectroscopic characterization, al-
though evidence of product distribution was obtained by
GC–MS. For the acyclic a-diimines studied, 10 and 11,
the product distribution was independent of the solvent,
but not the relative concentrations. When 0.001 M 11 in
benzene was irradiated for 49 h in the presence of TPP,
the chromatogram shown in Figure 3a was obtained with
the mass spectrometer in the electron impact (EI+) opera-
tion mode. Two major peaks are observed, along with two
secondary reaction products. Unreacted 11 corresponds to
the main peak with a retention time of 22.79 min (Fig. 3b
shows the EI+ mass spectrum of 11).38 Analyses of the pos-
itive chemical ionization (CI+) (not included) and the EI+
mass spectra (Fig. 3e) corresponding to peak with retention
time of 25.03 min, indicate that the main photooxidation
product in benzene was N-(4-methoxyphenyl)-2-[(4-meth-
oxyphenyl)imino]propanamide (11c). The peaks at 8.54
and 15.22 min suggest that 1-isocyano-4-methoxybenzene
(11a) and N-(4-methoxyphenyl)acetamide (11b) are sec-
ondary products of the photooxidation of 11 in benzene
(Scheme 3).
Diethyl ether
Table 4. LSER correlation equations for the reaction of singlet oxygen with
1,4-diaza-1,4-bis(p-methoxyphenyl)-2,3-dimethyl-1,3-butadiene (11)
2
log k¼log ko+sp*+dd+aa+bb+hrH
log ko
5.114
0.058
s
D
a
b
h
Coeff.
ꢃ
0.592
0.085
6.945
—
—
—
—
—
ꢀ0.597
—
—
—
—
—
0.003
0.001
4.746
0.0002
2.208
0.050
t-Stat.
87.440
ꢀ11.867
<0.0001
1.553
P(2-tail) <0.0001
VIF
<0.0001
1.647
—
N¼20, R¼0.975, SD¼0.079, F¼103.392
In all statistical tests performed for compound 10 including
simple linear regression, forward and backward ANOVA test
and multiple regression, only we found dependence with the
Hildebrand parameter. The correlation shows a coefficient h
equal to 0.003, with a regression coefficient between 0.6 and
0.75 (highly dependent on the number of data points consid-
ered) and a Fisher index near to 10. Although non-acceptable
statistical parameters are found, we believe that the total rate
constant for this compound depends primarily on the solvent
cohesive energy and the poor correlation is due to the narrow
range of kT values.
Figure 3c and d shows mass spectra ionization patterns and
the corresponding proposed structures. In the same way that
we previously described, we determined the formation of
formaldehyde (12) as one of the photooxidation products.
The same experiment carried out in propylencarbonate
yields 1-isocyano-4-methoxybenzene (11a) and N-(4-
methoxyphenyl)acetamide (11b) as main products whereas
the product with retention time equal to 25.03 is the minor
product. A similar behaviour was observed for 10. Photo-
oxidation in benzene yields N-phenyl-2-(phenylimino)pro-
panamide (10c) as the main product. In propylencarbonate,
the main reaction products were the 1-isocyano (10a) and
acetamide derivatives (10b).
2.4. Chemical reaction of singlet oxygen
with acyclic a-diimines
Chemical rate constants for reactions of acyclic a-diimines
with singlet oxygen were determined in steady-state experi-
ments by irradiating 0.001 M substrate in benzene or propy-
lencarbonate solutions with TPP as the sensitizer. GC-NPD
was used to monitor the substrate consumption (up to 30%).
In these experiments, 9,10-dimethylanthracene (DMA, kR
(benzene)37¼2.1ꢅ107 Mꢀ1 sꢀ1)was usedastheactinometer.
The values for kR calculated with Eq. 7 are summarized in
Table 5.
3. Discussion
3.1. Cyclic a-diimines
The quenching of singlet oxygen by 5 has been discussed
earlier by Gollnick et al.27 Product distribution was explained
in terms of a hydroperoxide intermediate resulting from the
rearrangement of a primary reaction intermediate, ‘perni-
trone’ or ‘nitrone oxide’ (13) (Scheme 4). Other possible
reaction pathways, involving interaction of singlet oxygen
with C-5 of the dihydropyrazine to give hydroperoxides
The data in Table 5 show that chemical rate constant in-
creases when solvent is changed from benzene to propylen-
carbonate. Comparison of kR values with kT values shows

10740
E. Lemp et al. / Tetrahedron 62 (2006) 10734–10746
Figure 3. (a) GC–MS chromatogram of 1 mM 1,4-diaza-1,4-bis(p-methoxyphenyl)-2,3-dimethyl-1,3-butadiene (11) in benzene after 49 h of irradiation in the
presence of TPP; (b) EI+ mass spectrum of 11; (c) EI+ mass spectrum of compound with retention time 8.54 min; (d) EI+ mass spectrum of compound with
retention time 15.22 min; (e) EI+ mass spectrum of compound with retention time 25.03 min.
(15) or addition of O2(1Dg) to the C]N double bond giving
peroxaziridines (16) were disregarded on the basis of ob-
served products.
highly dependent on solvent properties (Table 1). A mean-
ingful interpretation of kT solvent dependence was obtained
by using LSER solvatochromic equation. LSER correlations
listed in Table 2 indicate that the singlet oxygen reaction
with 5 has a different solvent dependence compared to that
found for with other compounds. For 5, the reaction rate
Kinetic results obtained in this work indicate that kT values
for singlet oxygen quenching by dihydropyrazines are

E. Lemp et al. / Tetrahedron 62 (2006) 10734–10746
10741
O
H3C
NH
N
O
R
H3C
N R
+
C
h
-
+
R
+
C
N
R
NH
H3C
HCHO +
benzene, TPP
R
R
N
CH3
12
P
Q
S
T
R
P
Q
S
T
10 10a 10b 10c
11 11a 11b 11c
CH3-O-
Scheme 3.
CH3
CH3
CH3
CH3
increases by more than 2 orders of magnitude when the
solvent is changed from non-polar (e.g., hexane) to polar
(e.g., propylencarbonate).28 The contribution of the chemi-
cal reaction in non-polar solvents is negligible, whereas in
highly polar solvents it represents the main deactivation
channel. Solvent dependence of kR can be explained if inter-
mediates along the reaction coordinate have more localized
charge than the initial complex. This result is compatible
with involvement of ion pairs in controlling the final product
distribution as depicted in Scheme 5.
N
13
N+
O
O
N
N
14
O+
CH3
CH3
N
O2 (1
)
g
O
N
5
CH3
N
N
The kT value for reactions of 6 and 8 with singlet oxygen is
substantially larger compared to 5, in most solvents. The kT
value for 7 is comparable or slightly larger than that of 5.
Solvent effects for 6, 7 and 8 analyzed in terms of LSER
are characterized by Hildebrand parameter dependence of
kT. Dependence of rate constant on Hildebrand parameter
has been ascribed to O2(1Dg) reactions, which involve a con-
certed or partially concerted cycloaddition of singlet oxygen
to an activated diene.11 The dependence on the Hildebrand
parameter is explained in terms of formation of an encounter
complex of smaller molecular volume compared to the
parent compounds. Furthermore, these reactions are also
affected by solvent dipolarity–polarizability. Moreover,
examination of LSER equations for 6, 7 and 8 shows that
the reaction is also assisted by HBA and inhibited by HBD
solvents. These results can be explained if phenyl substitu-
tion opens a further reactive channel in which the perepoxide
is stabilized by interaction with the p system of a phenyl
group.28,51 A reaction mechanism compatible with our
results is depicted in Scheme 6.
15
CH3
OOH
CH3
CH3
N
N
16
O
O
Scheme 4.
increases in solvents with higher capabilities to stabilize
charges and dipoles, and decreases in strong hydrogen bond
donor solvents. Data are compatible with an exciplex forma-
tion with considerable charge separation. This result could be
in agreement with the formation of both perepoxide (14) and
zwitterionic (13) intermediates as proposed by Gollnick
et al.27 Formation of these species as intermediates, in the
ene reaction of singlet oxygen with alkenes, prior to the prod-
uct determining step has been extensively discussed,39–49
although recent theoretical studies predict two adjacent
transition states without an intervening intermediate.50
Reaction path (a), leads only to physical quenching through
intersystem crossing to produce oxygen and the parent a-di-
imine. The geometry of the exciplex hinders intramolecular
hydrogen abstraction processes more that it stabilizes it.
Invoking the perepoxide structure (Scheme 6a) provides an
explanation for the observed solvent dependence. Decrease
of total reaction rate constants in HBD solvents can be un-
derstood in terms of interactions with the reactive centre
(the phenyl substituted C]N double bond). Furthermore,
the increase in sensitivity to HBA solvents may be due to
electrostatic stabilizing interactions with a positive charge
on the complex. In addition, dependence of kT on the Hilde-
brand parameter can be understood in terms of a phenyl
group–perepoxide interaction. This interaction would be
favourable in solvents with high cohesive energy because in-
teraction of negatively charged oxygen with the neighbour-
ing phenyl disrupts solvent–phenyl group interactions in the
substrate. In addition, this hypothesis permits us to explain
the low values of the chemical reaction constant measured
Our results support the formation of a perepoxide as the pri-
mary intermediate arising from the interaction between sin-
glet oxygen and 5. The LSER equation for this compound
shows that the relative statistical weight of the coefficient as-
sociated with the a parameter is smaller than the generally
observed for electrophilic attack of singlet oxygen on a nitro-
gen lone pair in amino compounds. This result implies steric
hindrance as a factor, likely due to hydrogen bonding be-
tween solvent and the nitrogen atom, inhibiting the reaction
but not in the extent observed with tertiary amines.2,17 This
result could be understood if nitrogen is not the reactive cen-
tre but is close to it. In the same way, we also found that the
coefficient associated with the p* parameter is larger than
that of reactions of O2(1Dg) with amines. Solvent depen-
dence on kR for reaction of 5 with O2(1Dg) is more significant
than that observed for kT. The chemical rate constant

10742
E. Lemp et al. / Tetrahedron 62 (2006) 10734–10746
R
O
R
NH C
N C
OH
+
HCHO
12
-
+
-
+
N
C
N
C
Y
+
R
N
N
N C
R
+
-
OH
O
HCHO
+
12
HO
-
+
N
N
R
N
N
R
N
C
CH2
R
CH2
+
OOH
CH3
N
N
OH
+ O
-
N C
R
+
OH
O
-
O
O
-
+
+
CH2
14
N
C
CH2
R
N C
+
CHO
H2O
+
-
N
C
Z
R
X
5
6
8
Y
Z
CH3
5a 5b
6a 6b
8a 8b
CH3-O-
Scheme 5.
O
O
R
N
R
(a)
Physical quenching
N
N
N
CH3
O2(1
)
R
+
g
CH3
N
(b)
Products and/or
Physical quenching
N
CH3
O
O
Scheme 6.
for 6 and 8 even in polar solvents and the absence of photo-
oxidation products for 7 and 9. As mentioned above, the only
reaction products detected for 6 and 8 arise from singlet
oxygen attack on a methyl substituted N–C double bond.
The total reaction rate constant for 6 and 8 is larger than
for the dimethyl substituted analogs. These data are consis-
tent with the mechanism of sensitized photooxidation of 6
proposed in Scheme 6. The increased reactivity of 6 and 8
towards singlet oxygen, relative to the dimethyl substituted
a-diimine (5), implies that the main path of reaction involves
the interaction of O2(1Dg) with the phenyl substituted N–C
double bond, to give a perepoxide-like exciplex that exclu-
sively evolves by intersystem crossing since there is no
any accessible a-hydrogen. Even though this mechanism
would be the only path for reaction of singlet oxygen with
8, this molecule is not much more reactive than 5. This
behaviour can be easily understood by considering results
of restricted DFT_B3LYP/6-311G* molecular modelling.
These calculations predict phenyl rings appreciably deviated
from the coplanarity regarding the imino double bond. For 5
we found a dihedral angle of 39.7ꢇ between the phenyl and
imino groups, while in the diphenyl substituted compound,
7, the dihedral angle increases to 56.6ꢇ, due to the larger ste-
ric hindrance between the phenyl rings. If exciplex leading
to physical quenching in Scheme 6 is considered, it can be
noticed that a larger dihedral angle between the imino
bond and the phenyl substituent would diminish the stabiliz-
ing interaction between the partially negative oxygen and the
p system of the phenyl substituent, and consequently lower
total rate constants would be expected. Compound 9 was the
cyclic a-diimine that exhibits the smallest solvent effect.
The LSER analysis for this compound shows that the reac-
tion is assisted by HBA and inhibited by HBD solvents.
This dependence on the microscopic solvent parameters
was similar to that observed for 6, 7 and 8 but kT for 9 was
found independent on the Hildebrand parameter. This be-
haviour can be explained by the effect of p-methoxyphenyl
substituent. Important resonant electron donor effects cannot

E. Lemp et al. / Tetrahedron 62 (2006) 10734–10746
10743
be expected due to the lack of coplanarity among the imino
and phenyl groups, on the contrary, the inductive electron
acceptor effect would be predominant. This effect, more
important for the methoxyphenyl group than the phenyl
group,39 diminishes the electron density on the imino bond
and increases the negative charge on the phenyl ring p sys-
tem, restricting both, the easiness of singlet oxygen electro-
philic attack and the stabilizing interaction between the p
system and the negative oxygen once the exciplex is formed.
The effect permits us to explain the larger reactivity of 6 and
7 in comparison to the reactivity of 8 and 9, respectively.
separation, as shown in Scheme 7. Second, reactivity of
acyclic a-diimines is dependent on resonant effects of p-sub-
stituent in the phenyl group. The large resonant electron
donor capacity of p-methoxy substituent in 11 increases
the reactivity of this compound relative to the non-
substituted 10.
A concerted or partially concerted cycloaddition reaction
mode would allow us to rationalize product distribution
over extended periods of time in photooxidation experi-
ments and similarly explain the dependence on solvent
polarity. Identical product distributions are found in polar
and non-polar solvents, but their relative concentrations
change according to the media. This implies that at least
two different intermediates lead to the detected products.
The first intermediate may be highly favoured in polar sol-
vents because of larger kR values in these solvents. The inter-
mediate could then rearrange to a non-polar intermediate in
non-polar solvents. Scheme 8 shows a mechanism explain-
ing these results.
3.2. Acyclic a-diimines
Theoretical calculations predict a trans configuration of the
two coplanar imino bonds as the most probable structure,
with the phenyl substituents on the nitrogen slightly out of
the plane due to steric interactions with methyl groups in po-
sitions 2 and 3. This configuration does not permit an even-
tual [2+4] cycloaddition of singlet oxygen to the conjugated
double bonds. As mentioned above, the reactivity of acyclic
a-diimines towards singlet oxygen is lower than that for the
cyclic homologous by a factor 10–100, probably because of
the most flexible linear structure. In addition, the data show
kT values strongly dependent on phenyl ring substituent, be-
ing more reactive than the p-methoxy substituted compound.
The kT values for 11 increase in solvents both with larger
capacity to stabilize charges and dipoles, and with high
cohesive energy. Also, they decrease in strong HBD solvents
(Table 4). The dependence on the p* parameter implies the
formation of an exciplex with appreciable charge separation.
Furthermore, the dependence on r2H means a more compact
exciplex than the parent compounds. This dependence is
similar to that found for reaction of O2(1Dg) with 1,4-di-
methylnaphthalene.11 In this case, a partially concerted
cycloaddition mechanism has been suggested to account
for the dependence of the rate constant with solvent micro-
scopic parameters. For 11 reaction with O2(1Dg), a partially
concerted [2+2] cycloaddition, as shown in Scheme 7 is
proposed to account for kT dependence on the solvent.
Decrease of kT in HBD solvents can be explained in terms
of interaction of acidic solvents with the nitrogen lone
pair, which sterically hinders the access of excited oxygen
to the reactive centre.
In Scheme 8, path (a) accounts for 1-isocyano-4-methoxy-
benzene (11a) and N-(4-methoxyphenyl)acetamide (11b),
the main products observed in the photooxygenation of 11
in propylencarbonate. Path (b) explains the smaller reactiv-
ity in benzene as solvent and the increase in N-phenyl-2-
(phenylimino)propanamide (11c) relative concentration. A
similar mechanism has been proposed by Ito et al.23 to
explain product distribution in sensitized oxidation of
hydrazones.
3.3. Conclusions
The 5,6-disubstituted cyclic a-diimines are moderate to effi-
cient singlet oxygen quenchers, and are most effective in
polar solvents. A reaction mechanism involving a perepoxide
intermediate that forms a hydroperoxide appears to be the
main reaction path from which the products arise. The re-
placement of a phenyl substituent with a methyl substituent
opens an additional reaction path involving a perepoxide-
like exciplex in which a stabilizing interaction of the nega-
tive charge on the free oxygen of a perepoxide with aromatic
p system contributes to an increased singlet oxygen quench-
ing ability of cyclic a-diimines. 1,4-Disubstituted acyclic
a-diimines are moderate to poor singlet oxygen quenchers.
The total rate constants are scarcely dependent on the
solvent properties. A reaction mechanism involving a
dioxetane-like exciplex that evolves to a charged intermedi-
ate from which products are formed is most likely the main
reaction path in polar solvents.
The lower reactivity of 10, the reduced solvent effect on kT
and the dependence of kT on the Hildebrand parameter in
spite of the poor correlation can be interpreted based on
two factors. First, the exciplex for this compound is formed
through a concerted [2+2] cycloaddition with no charge
+
C N
OMe
C N
OMe
1O2 MeO
N C
MeO
N C
+
O
O
11
C N
C N
N C
1O2
+
N C
O
O
10
Scheme 7.

10744
E. Lemp et al. / Tetrahedron 62 (2006) 10734–10746
R
O
OH
CH2+
O
N
-
C+
+
H3C
N
HCHO +
H3C
NH
R
(a)
OH
R
N
R
R
R
N
H3C
N
R
12
Q
O
S
HOO-
+
O
N
CH3
CH2
H3C
N
R
H3C
N
R
R
R
O
(b)
O
P
NH
CH2
NH
O
HCHO +
H3C
N
R
H3C
N
R
T
R
P
Q
S
T
10 10a 10b 10c
11 11a 11b 11c
CH3-O-
Scheme 8.
4. Experimental
solution was irradiated in the presence of the sensitizer up
tow30 to 40% conversion. At least six duplicate 50 mL sam-
ples at different time intervals were taken for GC analysis.
DMA was used as actinometer.
4.1. General
Melting points (not corrected) were determined employing
both a modified Koffler and a Electrothermal 9200 appara-
tus. NMR spectra were obtained from a Bruker DRX-300
spectrometer. Chemical shifts are referred to internal tetra-
methylsilane, TMS. Elemental analyses were performed
on a Fisons EA 1108 instrument. IR spectra were obtained
on a Fourier transform Bruker IFS-56 spectrometer. UV–
vis measurements were made in a Unicam UV-4 spectropho-
tometer. A Fisons MD-800 GC–MS system with a Hewlett
Packard Ultra-2 capillary column (25 m) was used to obtain
electron impact mass spectra. All spectroscopic measure-
ments were performed at room temperature.
Time-resolved luminescence measurements were carried
out in 1 cm path fluorescence cells. TPP or RB were
excited by the second harmonic (532 nm, ca. 9 mJ per pulse)
of 6-ns light pulse of a Quantel Brilliant Q-Switched
Nd:YAG laser. A liquid-nitrogen cooled North Coast model
EO-817P germanium photodiode detector with a built-in
preamplifier was used to detect infrared radiation from the
cell. Detector was coupled to the cell at right angle. An
interference filter (1270 nm, Spectrogon US, Inc.) and a
cut-off filter (995 nm, Andover Corp.) were the only
elements between cell face and the diode cover plate. Pre-
amplifier output was fed into the 1 MU input of a digitizing
oscilloscope Hewlett Packard model 54540 A. Computerized
experiment control, data acquisition and analysis were per-
formed with a LabView based software developed in our
laboratory.
4.2. Materials
All solvents used in the synthesis were of reagent grade. In
spectroscopic and kinetic measurements, spectroscopic or
HPLC quality solvents were used. 5,10,15,20-Tetraphenyl-
21H,23H-porphine (TPP), 99%, and 9,10-dimethyl-anthra-
cene, (DMA), 99%, from Aldrich were used without further
purification. Rose Bengal (RB), 96%, from Fluka, was
recrystallized twice from ethanol prior to use.
Restricted density functional theory calculations were made
using Gaussian 03W software. All structures were geometry
optimized at the B3LYP/6-311G* level.
Equation coefficients and statistical parameters of LSER and
TLSER correlations were obtained by multilinear correla-
tion analysis with STAT VIEW 5.0 (SAS Institute Inc.).
Results agreed with the t-statistic of descriptors.
4.3. Methods
Chemical reaction rate constants were determined in several
selected solvents using a 10 ml double wall cell, light-pro-
tected by black paint. A centred window allowed irradiation
with light of a given wavelength using Schott cut-off filters.
Circulating water maintained the cell temperature at
22ꢃ0.5 ꢇC. Sensitizer irradiation, RB or TPP was performed
with a visible, 200 W, Par lamp. A Hewlett Packard 5890 gas
chromatograph equipped with a NPD detector and a Hewlett
Packard Ultra-2 capillary column was used to monitor sub-
strate consumption. In a typical run, 0.001 M substrate
4.4. Chemical synthesis
4.4.1. Synthesis of cyclic a-diimines. 5,6-Disubstituted-
2,3-dihydropyrazines were synthesized as previously
described.52 Typically, a solution of the corresponding di-
ketone (5 g) in ethyl ether (10 ml) was added to ethylendi-
amine (2 g) in 10 ml of ethyl ether maintained at 0 ꢇC. The
mixture was refluxed for 30 min and the ethereal solution

E. Lemp et al. / Tetrahedron 62 (2006) 10734–10746
10745
was dried over sodium sulfate and solvent removed in
vacuum. The remaining oil was cooled in a freezer during
several hours producing a solid from which pure 5,6-disub-
stituted-2,3-dihydropyrazine was obtained as yellow needles
by recrystallization from ethyl ether–hexane.
solid. The solid was filtered, washed with cold ethanol and
recrystallized from ethanol to obtain the pure product.
4.4.2.1. 1,4-Diaza-1,4-diphenyl-2,3-dimethyl-1,3-buta-
diene (10). This compound was prepared in 49% yield
from aniline according to the already described procedure;
mp 137–139 ꢇC (lit.54 mp 136–137 ꢇC). 1H NMR (CDCl3):
d 2.15 ppm (s, 6H), 6.77–6.81 ppm (m, 2H), 7.08–
7.14 ppm (m, 1H), 7.33–7.40 ppm (m, 2H). IR (KBr, n,
cmꢀ1): 3058, 1634, 1590, 1480, 1445. MS m/e¼236 (M+),
118, 103, 77, 51. Elem. anal. calcd %C: 81.35, %H: 6.78,
%N: 11.86; exp. %C: 81.14, %H: 7.02, %N: 12.22.
4.4.1.1. 5-Methyl-6-phenyl-2,3-dihydropyrazine (6).
This compound was prepared in 50% yield from 1-phenyl-
1,2-propanedione according to the already described proce-
dure; mp 34–37 ꢇC (lit.27,53 mp 38–39 ꢇC). 1H NMR
(CDCl3): d 2.1 ppm (s, 3H), 3.35–3.55 ppm (m, 4H), 7.3–
7.4 (m, 5H). IR (KBr, n, cmꢀ1): 2944, 2833, 1636, 1569,
1440. MS m/e¼172 (M+), 157, 131, 103, 77.
4.4.2.2. 1,4-Diaza-1,4-bis(p-methoxyphenyl)-2,3-di-
methyl-1,3-butadiene (11). In a reaction similar to that
of DPDM, 3.8 g (31 mmol) of p-anisidine and 1.2 g
(14 mmol) of 2,3-butanedione yields 52% of DMPDM;
4.4.1.2. 5,6-Dimethyl-2,3-dihydropyrazine (5). Following
the procedure for the preparation of MPD, the condensation
reaction between ethylendiamine and 2,3-butanedione
afforded a liquid reaction crude. Careful distillation under
nitrogen was required to obtain pure DMD, yield 40%, bp
58 ꢇC (15 mmHg) (lit.52,53 bp 53–54 ꢇC (12 Torr), 60–62 ꢇC
1
mp 185–186 ꢇC. H NMR (CDCl3): d 2.18 ppm (s, 6H),
3.82 ppm (s, 6H), 6.78 ppm (d, 2H), 6.91 ppm (d, 2H). IR
(KBr, n, cmꢀ1): 2960, 1633, 1501, 1469. MS m/e¼296
(M+), 281, 148, 92, 77. Elem. anal. calcd %C: 72.97, %H:
6.76, %N: 9.46; exp. %C: 72.67, %H: 7.01, %N: 9.48.
1
(18 Torr)). H NMR (CDCl3): d 1.87 ppm (s, 6H), 3.07 ppm
(s, 4H). IR (KBr, n, cmꢀ1): 2949, 2845, 1655, 1598, 1439.
MS m/e¼110 (M+), 95, 69, 54, 42.
Acknowledgements
4.4.1.3. 5,6-Diphenyl-2,3-dihydropyrazine (7). In a
reaction similar to that of DMD, 4.2 g (20 mmol) of benzyl
and 1.2 g (20 mmol) of ethylendiamine yields 85% of DPD;
mp 163–165 ꢇC (lit.27,53 mp 162.5–163.5 ꢇC). 1H NMR
(CDCl): d 3.72 ppm (s, 4H), 7.26–7.43 ppm (m, 10H). IR
(KBr, n, cmꢀ1): 2942, 2831, 1553, 1490. MS m/e¼234
(M+), 176, 131, 103, 77.
Financial support from FONDECYT (grant 2990096) and
Departamento de Postgrado de la Universidad de Chile
(grants PG/037/98 and PG/51/99) are gratefully acknow-
ledged.
References and notes
4.4.1.4. 5,6-Bis(p-methoxyphenyl)-2,3-dihydropyra-
zine (9). Following the same procedure to synthesize
DMD 2.2 g (8.3 mmol) of 4,40-dimethoxybenzyl and 0.5 g
(8.3 mmol) of ethylendiamine afforded a pale yellow solid,
after purification by employing a chromatographic column
packed with silica and chloroform as the eluent. Subsequent
recrystallization from ethanol yield 75% of pure BMPD; mp
127–129 ꢇC with dec. 1H NMR (CDCl3): d 3.56 ppm (s, 4H),
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133, 103, 77. Elem. anal. calcd %C: 73.47, %H: 6.12, %N:
9.52; exp. %C: 73.26, %H: 6.17, %N: 9.78.
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