Photo-dehydrogenation of 4,6-diaryl-2-oxo-1,2,3,4-tetrahydropyrimidines

Article abstract of DOI:10.1007/s13738-017-1084-2

Electron-transfer-induced photo-oxidation of 4,6-diaryl-substituted 2-oxo-1,2,3,4-tetrahydropyrimidines (THPMs) in chloroform under argon atmosphere results in the smooth formation of 4,6-diaryl-substituted 2-oxo-1,2-dihydropyrimidines. Sequentially, elec

Full text of DOI:10.1007/s13738-017-1084-2

J IRAN CHEM SOC
DOI 10.1007/s13738-017-1084-2
ORIGINAL PAPER
Photo‑dehydrogenation
of 4,6‑diaryl‑2‑oxo‑1,2,3,4‑tetrahydropyrimidines
Hamid Reza Memarian1 · Esmael Sanchooli1
Received: 22 November 2016 / Accepted: 13 February 2017
© Iranian Chemical Society 2017
Abstract Electron-transfer-induced photo-oxidation of
4,6-diaryl-substituted 2-oxo-1,2,3,4-tetrahydropyrimidines
(THPMs) in chloroform under argon atmosphere results
in the smooth formation of 4,6-diaryl-substituted 2-oxo-
1,2-dihydropyrimidines. Sequentially, electron-transfer and
proton removal processes in this oxidative reaction result
in the occurrence of two different benzylic and allylic radi-
cal intermediates, which converted to each other via reso-
nance. Preferably, capto-dative stabilized radical center
stimulates the type of product. Based on the proposed oxi-
dation reaction mechanism, the electron transfer from the
excited THPMs to chloroform starts this oxidative reaction.
The results of the computational study obtained at DFT-
B3LYP/6-311++G** level of theory indicate that the first
electron is preferably removed from the N1 atom of the het-
erocyclic ring. A comparison of the sum of the Mulliken
spin densities of the radical intermediates supports the
argument that the more stable capto-dative stabilized radi-
cal is involved in the reaction.
Introduction
The nitrogen-containing heterocyclic compounds, 2-oxo-
1,2,3,4-tetrahydropyrimidines (THPMs) or dihydropyrimi-
dinones, also known as Biginelli compounds were reported
over one hundred years ago [1]. Biological and pharmaco-
logical activities of THPMs and 2-oxo-1,2-dihydropyrimi-
dines (DHPMs) or 2-pyrimidinones (oxidized derivatives of
THPMs) are known [2–7]. These activities for 5-unsubsti-
tuted THPMs known as Biginelli-like compounds and cor-
responding dehydro-compounds have also been observed
[8, 9].
Our previous studies were concentrated on the investi-
gation of the steric and electronic effects of the heterocy-
clic ring substitutions on the 4- and 5-positions of various
THPMs (Scheme 1) on the rate of photochemical [10–13]
and thermal [14–16] oxidation process, and voltammetric
measurements [17]. The results of all these investigations
elucidate the importance of the electronic effects of 4-sub-
stitution over those of 5-substitution.
Keywords Light-induced Oxidation · DFT · Capto-
dative stabilization · Electron transfer · Substituent effect ·
Tetrahydropyrimidines
On the basis of the proposed mechanism for the photo-
oxidation of THPMs in chloroform solvent [10, 11], the
excited molecule (THPMs*) donates an electron prefer-
ably from the N1-position of the heterocyclic ring to chlo-
roform as an electron-acceptor species (electron-transfer
process = ET) under formation of the radical cation and
radical anion intermediates, THPMs·+ and CHCl3·−, respec-
tively. Elimination of HCl molecule from these species
leads to the formation of trihydropyrimidyl (TrHPMs·) and
dichloromethyl (·CHCl2) radicals. Due to delocalization of
the single electron in the trihydropyrimidyl radical inter-
mediate (TrHPM·), this species is considered as benzylic/
allylic and allylic radicals, which is converted to each other
via resonance. Further removal of the second hydrogen
atom from 3-NH position of more stable benzylic/allylic
Electronic supplementary material The online version of this
article (doi:10.1007/s13738-017-1084-2) contains supplementary
material, which is available to authorized users.
* Hamid Reza Memarian
memarian@sci.ui.ac.ir
1
Department of Chemistry, University of Isfahan,
Isfahan 81746-73441, Islamic Republic of Iran
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J IRAN CHEM SOC
of this species, two different benzylic and also allylic radi-
cal intermediates are formed, which are converted again to
each other via resonance. The second hydrogen removal
is expected to occur from more stable and involved radi-
cal intermediate, which leads to the formation of the final
DHPM. Possible formations of two different DHPMs,
namely DHPM (4-Ar1/6-Ar2) and/or DHPM (6-Ar1/4-
Ar2), are expected in the present study depending on the
preferred involvement of the benzylic/allylic radical (4) or
benzylic/allylic radical (6), respectively (Scheme 3).
Scheme 1 Oxidation of 2-oxo-1,2,3,4-tetrahydropyrimidines
(THPMs)
Results and discussion
radical intermediate results in the formation of 2-oxo-
1,2-dihydropyrimidines (DHPM) (Scheme 2).
In order to elucidate the effect of the oxygen or argon
atmosphere on the outcome of the photoreaction, irradia-
tion of compound 1a as representative carried out in air-
saturated chloroform as solvent, under oxygen and argon
atmosphere by bubbling oxygen or argon in the reaction
vessel during the irradiation. Whereas TLC monitoring
of the reaction mixture in air-saturated chloroform and
Considering these steric and electronic effects of the
substituent on the electron-donating ability of the hetero-
cyclic ring toward the electron-acceptor species and based
on the above-mentioned mechanism, after the formation of
the radical cation species (THPM·+) from 4,6-diaryl-2-oxo-
1,2,3,4-tetrahydropyrimidines and following deprotonation
Scheme 2 Electron-transfer-induced oxidation of 2-oxo-1,2,3,4-tetrahydropyrimidines involving benzylic/allylic and allylic radical intermedi-
ates
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J IRAN CHEM SOC
Scheme 3 Involvement of two different benzylic/allylic radical intermediates in the oxidation of 4,6-diaryl-2-oxo-1,2,3,4-tetrahydropyrimidines
Scheme 4 Photo-oxidation
of 4,6-diaryl-2-oxo-1,2,3,4-
tetrahydropyrimidines
under oxygen atmosphere confirmed the formation of the
oxidation product 2a accompanied with trace amount of
unidentified products, a clean reaction under formation
of the sole product 2a observed by carrying the irradia-
tion under argon atmosphere. The results indicate also
that the presence of the oxygen atmosphere accelerates
the reaction. Therefore, a 0.004 M solution of each of
4,6-diaryl-2-oxo-1,2,3,4-tetrahydropyrimidines (1a–1g)
in chloroform solvent was irradiated under argon atmos-
phere until total disappearance of 1a–1g as monitored by
TLC (Scheme 4). The results are presented in Table 1.
The results presented in Table 1 indicate that upon
oxidation of 1a–1g and removal of two hydrogens from
4-position and 1- or 3-positions of the heterocyclic ring,
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J IRAN CHEM SOC
Time (min)a
Table 1 Photo-oxidation
of 4,6-diaryl-2-oxo-1,2,3,4-
tetrahydropyrimidines (THPMs,
1a–1g) in chloroform solvent
under argon atmosphere to
2-oxo-1,2-dihydropyrimidines
(DHPMs)
THPM
X
Y
DHPM
X
Y
1a
1b
1c
1d
1e
1f
H
H
2a
H
H
H
H
H
H
H
H
86
40
50
55
45
60
50
4-CH3O
3-CH3O
2-CH3O
H
H
3b
4-CH3O
3-CH3O
2-CH3O
4-CH3O
3-CH3O
2-CH3O
H
3c
H
3d
4-CH3O
3-CH3O
2-CH3O
3bb
3cc
3dd
H
1g
H
a
The times are given after total disappearance of 1a–1g (100% conversion according to TLC observation)
b–d
These products are also obtained by the photo-oxidation of 1e–1g, respectively
dihydropyrimidin-2-one products are formed. Whereas the
irradiation of 1a results in the formation of the photoprod-
uct 2a, the same as 3a, irradiation of 1b–1g causes the for-
The interesting results of the present study, as already
mentioned, are obtaining the same products 3b–3d by
irradiation of either 1b or 1e, either 1c or 1f, and either 1d
or 1g, respectively. The difference between the starting
materials is the location of the methoxy-substituted phe-
nyl ring either on the 4- or 6-positions of the heterocyclic
ring. Due to the mentioned difference in absorption, the
UV spectra of 1b and 1e containing the 4-methoxyphenyl
group on the 4- and 6-positions of the heterocyclic ring,
respectively, are given as representative in Fig. 2 (left),
which indicates clearly different UV absorptions of 1b
and 1e. In contrast to these observations, the UV spectra
of the corresponding photoproducts illustrated in Fig. 2
(right) are very similar and indicates the formation of the
similar product upon oxidation of different starting mate-
rials. The remaining UV spectra are presented as support-
ing materials.
1
mation of 3b–3d. UV, IR, H NMR and 13C NMR spec-
troscopic data gave useful information about the structural
assignment of the photoproducts, especially the similarity
of the photoproduct 3b obtained by irradiation of either 1b
or 1e, and 3c from 1c or 1f and finally 3d from 1d or 1g.
Some of these spectra are presented here, and the remain-
ing spectra are provided in the supporting materials.
The maximum absorption in the UV spectra of 4,6-dia-
ryl-2-oxo-1,2,3,4-tetrahydropyrimidines appears in the
lower wavelengths in comparison with those of the oxida-
tion products. Formation of the semi-aromatic heterocyclic
ring containing the amino-conjugated dienone system leads
to an extended conjugation toward 2-CO group. Conse-
quently, a decrease in the π and π* levels and bathochro-
mic shifts accompanied with the hyperchromic effect in the
UV spectra are observed. These phenomena are presented
in Fig. 1, as representative by comparison of the UV spec-
tra of 1a and corresponding photoproduct 2a.
The effective extended conjugation in the heterocyclic
ring is not only supported by these UV absorptions, but
also by calculation of the dipole moment (μ) of 1a–1g
and the oxidation products based on the DFT calcula-
tion given in Table 2. These data support the argument
that due to the formation of the semi-aromatic hetero-
cyclic ring, the electron delocalization of the N1 lone
pair toward the 2-CO group is increased; therefore, the
enhancement of the dipolar nature of the heterocyclic
ring and an increase in the value of the dipole moment
are expected.
Fig. 1 UV spectra of compound 1a and corresponding oxidation
product 2a
Table 2 Dipole moment (μ)
Comp.
1a
1b
1c
1d
1e
1f
1g
of compounds 1a–1g and the
oxidation compounds 2a, 3b–3d
calculated by B3LYP/6-31++G
(d,p) method
μ (Debye)
Comp.
4.22
2a
4.30
3b
3.63
3c
4.14
3d
5.68
5.10
4.33
3e = 3b
7.81
3f = 3c
6.10
3g = 3d
7.95
μ (Debye)
7.28
7.81
6.11
7.97
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J IRAN CHEM SOC
Fig. 2 UV spectra of compound 1b and 1e (left), and corresponding oxidation products 3b and 3e = 3b (right)
The most useful information for the characterization of
the photoproducts obtained by comparison of the 1H NMR
spectra of 1a–1g and their photoproducts 2a and 3b–3d is
described below:
data support the results of photo-oxidation of THPMs con-
sidered in the present study.
Mechanistic studies
1
• In H NMR spectra of 1a–1g, characteristic absorption
of 5-CH, 3-NH and 1-NH protons appeared around 5.1,
7.2 and 8.5 ppm, respectively. Upon photo-oxidation,
the loss of two hydrogen atoms, namely one hydrogen
atom from the 4-position of the heterocyclic ring and
another hydrogen atom either from 1-NH or 3-NH posi-
tions, is observed.
In order to elucidate the electronic effect of C4- and C6-aryl
substitutions on the irradiation time especially for a very
closed reaction time in the present study, the reactions of
1b and 1e containing the para-methoxyphenyl substituent
on the 4- and 6-positions of the heterocyclic ring, respec-
tively, were followed by UV spectroscopy. The UV reac-
tion spectra are presented in Fig. 4, and the corresponding
slope of the extinction versus time (ET diagram)1 at 370 nm
shows that the compound 1b has comparatively greater rate
constant of 5.7 × 10−2 mol L−1 s−1 than 1e with the rate
constant of 5.3 × 10−2 mol L−1 s−1. These data support the
observed shorter irradiation time of 40 min for total disap-
pearance of 1b compared to 45 min for compound 1e.
The results given in Table 1 indicate that the presence
of the methoxyphenyl substituent on the 4- or 6-position of
the heterocyclic ring facilitates the photo-oxidation process
compared to that of the parent molecule 1a. The electronic
effect of the methoxy-substituted phenyl ring on the short-
ening of the reaction time can be explained by considering
the reaction mechanism presented in Scheme 3. According
to the proposed mechanism, UV irradiation of the THPM
molecule leads to the promotion of the molecule to the
excited state (THPM*). The electron-transfer process (ET)
from the excited molecule as an electron-donating species
in the next step to chloroform molecule as an electron-
acceptor species causes the formation of tetrahydropy-
rimidine radical cation (THPM·+) and chloroform radical
• Owing to the formation of the semi-aromatic heterocy-
clic ring in the photoproducts 2a and 3b–3d, the shift
of the absorption of remaining NH proton to lower field
(higher frequency) is observed, which is attributed to
the delocalization of the nitrogen lone pair toward the
extended azadiene system.
• Anisotropic effect of the semi-aromatic ring on the
5-CH proton causes the shift of its absorption to the aro-
matic region around 7.5 ppm.
• The hydrogen atoms of the methyl moiety of the meth-
oxy group in all photoproducts are shifted toward the
lower field. This is due to the formation of the amino-
conjugated dienone system and possible conjugation of
the oxygen lone pairs toward the aromatic ring.
• The formation of 3b–3d upon photo-oxidation of either
1b or 1e, either 1c or 1f and 1d or 1g was confirmed
1
by obtaining the same H NMR spectra of each pair of
photoproducts. These spectra are illustrated in Fig. 3 for
3b obtained upon photo-oxidation of either 1b or 1e.
Comparison of the infrared spectra of 1a–1g and the
photoproducts indicates a decrease in the NH peak inten-
sity and the shift of the 2-CO stretching to lower frequency.
Comparison of the 13C NMR spectra showed an increase
in peaks in the aromatic region and the lack of C4 peak in
region for the aliphatic carbons. All these spectroscopic
1
The absolute term “extinction” is a German word and has now been
replaced with “absorbance,” but the phrase “Extinction time” is still
using.
1 3

J IRAN CHEM SOC
e
M
O
H
N
H
H
N
4
5
6
3
H
4
N
H
5
6
3
N
O
2
1
O
2
H
Me
O
1
e
1
1b
e
M
O
N
6
4
5
6
3
H
O
N
5
1
N
H
3b
O
2
1
4
N
2
3
e
M
O
=
e
3
3b
Fig. 3 Comparison of the 1H NMR of compounds 1b, 1e, 3b and 3e=3b
Fig. 4 Reaction spectra of photochemical oxidation of 1b (left) and 1e (middle) in chloroform solvent and the corresponding extinction time
(ET) diagrams at 370 nm (time interval 8 min)
anion (CHCl·3−) intermediates, respectively. In the next
step, elimination of HCl molecule from both these inter-
mediates (C4–H removal accompanied with Cl−) produces
trihydropyrimidyl (TrHPM·) and dichloromethyl (CHCl·2)
radical intermediates. Finally, hydrogen removal from the
N1- or N3-positions of TrHPM· intermediate and forma-
tion of CH2Cl2 can possibly form the photoproduct DHPM
(4-Ar1/6-Ar2) and/or (6-Ar1/4-Ar2).
The methoxy group on each position of C4-aryl ring acts
as a σ-donor or σ-acceptor substituent due to the attachment
of the methoxy-substituted aryl ring with the sp3 hybrid-
ized C4-atom of the heterocyclic ring, whereas this group
behaves as a π-donor or π-acceptor due to the attachment
of the methoxy-substituted aryl ring with the sp2 hybridized
C6-atom of the heterocyclic ring. Coplanar orientation of
the methoxy group on the para- and ortho-positions with
the aryl ring results in the delocalization of its oxygen lone
pair toward the C-aryl ring (C8) attached to the C4-atom of
the heterocyclic ring (Scheme 5), acting the aryl ring as a
σ-donor substituent. Consequently, an increase in the elec-
tron density of the heterocyclic ring via σ-bond is expected,
which facilitates the electron removal from the N1-atom
compared to that of compound 1a containing the normal
phenyl ring on the 4-position.
The methoxy group in 1e–1g has different electron-
donor and electron-acceptor properties depending on its
location on the ortho- or para- and meta-positions, respec-
tively. These properties completely depend on the orienta-
tion of C6-aryl ring toward the C6=C5 double bond of the
heterocyclic ring. DFT calculations of 1e–1g show that due
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J IRAN CHEM SOC
Scheme 5 Electron-donating
of the 4-CH3OC6H4 group on
the C4-position in increasing the
electron density of the heterocy-
clic ring via the σ bond
Scheme 6 Participation of the oxygen lone pair in the CH3O group in 1e as representative via resonance (route 1) or inductive way (route 2) to
increase the electron density of the heterocyclic ring and showing the ortho-repulsion
to the observed ortho-repulsion, this co-planarity is not
possible; therefore, an effective π-delocalization toward the
heterocyclic ring is not expected (Scheme 6, route 1), and
the aryl group can act only as a σ-donor (Scheme 6, route
2).
In order to elucidate the steric and electronic effects
of the methoxy group on the electron-donor ability of the
aryl ring toward the heterocyclic ring, cyclic voltammetric
measurements were carried out. The results presented in
Table 3 indicate that the substituted methoxyphenyl group
on both C4- and C6-positions causes a decrease in the oxi-
dation peak potential compared to that of the parent com-
pound 1a. These results are in agreement with the proposed
electron-transfer-induced photo-oxidation and the reduced
irradiation time given in Table 2 compared to that of 1a.
The results of the CV measurements of 5-carboethoxy
THPMs (Scheme 1, R=OC2H5) having the same aryl group
on the 4-position as in the present study are compared
with the CV data reported in the present work. These data
clearly indicate that by failure of 5-substitution in THPMs,
namely the electron-withdrawing carboethoxy group and
having only the hydrogen atom on this position, the oxida-
tion peak potential is lowered compared to those of 5-sub-
stituted THPMs [17]. On the other hand, a comparison of
the irradiation times of 5-substituted THPMs [10, 11] with
the results presented in this work elucidates the facile elec-
tron transfer of the excited molecule (THPMs*) toward
the electron-acceptor species chloroform in the absence
of 5-substitution and drastic decreasing of the irradiation
times.
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J IRAN CHEM SOC
Table 3 Comparison of
5-Unsubstituted THPMs
5-Carboethoxy THPMs
the oxidation peak potential
(Ep) versus ferrocene redox
potential (0.583 V), obtained
from cyclic voltammograms in
acetonitrile for THPMs (1a–1g)
and 5-carboethoxy-substituted
THPMs (E)
4-Position
6-Position
Ep
4-Position
6-Position
Ep
1a
1b
1c
1d
1e
1f
C6H5
C6H5
1.274
1.154
1.204
1.248
1.165
1.245
1.181
C6H5
CH3
CH3
CH3
CH3
1.513
1.464
1.472
1.365
4-CH3OC6H4
3-CH3OC6H4
2-CH3OC6H4
C6H5
C6H5
4-CH3OC6H4
3-CH3OC6H4
2-CH3OC6H4
C6H5
C6H5
4-CH3OC6H4
3-CH3OC6H4
2-CH3OC6H4
C6H5
1g
C6H5
Table 4 NBO spin densities
on the THPMs, radical cation
(THPM·+) and radical (TrHPM·)
Comp.
NI
C2
N3
C4
C5
C6
1a
−0.670
−0.568
−0.639
−0.669
−0.594
−0.643
−0.670
−0.592
−0.639
−0.670
−0.550
−0.641
−0.670
−0.599
−0.644
−0.668
−0.557
−0.640
−0.664
−0.562
−0.638
0.819
0.810
0.822
0.819
0.892
0.834
0.817
0.810
0.882
0.820
0.811
0.822
0.818
0.813
0.837
0.820
0.810
0.822
0.820
0.825
0.821
−0.680
−0.672
−0.639
−0.685
−0.666
−0.634
−0.679
−0.665
0.643
−0.081
−0.116
0.172
−0.279
−0.057
−0.286
−0.280
−0.132
−0.297
−0.276
−0.123
−0.284
−0.289
−0.049
−0.208
−0.287
−0.070
−0.290
−0.281
−0.043
−0.286
−0.286
−0.056
−0.289
0.166
0.259
0.166
0.167
0.253
0.162
0.164
0.268
0.165
0.171
0.225
0.165
0.170
0.245
0.170
0.169
0.256
0.165
0.175
0.254
0.165
1a·+
1a·
1b
1b·+
1b·
1c
−0.080
−0.103
0.180
−0.082
−0.106
0.166
1c·+
1c·
1d
−0.677
−0.647
−0.638
−0.678
−0.661
−0.642
−0.685
−0.655
−0.640
−0.683
−0.658
−0.640
−0.093
−0.134
0.166
1d·+
1d·
1e
1e·+
1e·
−0.082
−0.115
0.161
1f
−0.081
−0.120
0.166
1f·+
1f·
1g
−0.082
−0.118
0.165
1g·+
1g·
present study. In addition, natural bond orbital (NBO) anal-
ysis should explain the active position of the heterocyclic
ring in donation of the electron to chloroform.
Computational studies
The interesting results of the present study are that the
same photo-oxidation products is obtained from two dif-
ferent dispositional substitution in THPMs, namely the
photo-oxidation of 1b or 1e, 1c or 1f and 1d or 1g produce
the same photoproducts 3b–3d, respectively. In order to
elucidate this observation, especially to support the pro-
posed electron-transfer process in the photo-oxidation reac-
tion, computational studies were performed using Gauss-
ian 98 program package [18]. Density functional theory
(DFT) at the B3LYP/6-31++G (d,p) level has been used
to study structural, electronic and bonding characteristics
of THPMs, THPMs·+, TrHPMs· intermediates and the cor-
responding oxidation products (DHPMs) considered in the
Since the oxidation does not occur in the absence of
UV exposure, the electron transfer from excited molecule
THPM* to chloroform leads to the formation of THPM·+
and CHCl·3− intermediates, respectively. A comparison
of the natural bond orbital (NBO) results of THPM com-
pounds and corresponding THPM·+ intermediates pre-
sented in Table 4 indicates that the first electron removal
is occurred preferably from the N1-atom. This is explained
due to effective stabilization of the single electron on the
N1-atom of THPM(N1)·+ intermediate in conjugation
with the C6=C5 double bond (Scheme 7). Therefore, the
back electron-transfer process (BET) is more possible in
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J IRAN CHEM SOC
Scheme 7 Possible delocalization of the single electron in the N1 and N3 radical cation intermediates
THPM(N3)·+ intermediate due to failure of such effective
electron delocalization (Scheme 8).
attached π-system (via resonance) or the lone pair of the
neighboring heteroatom results in the stabilization of the
single electron. These interactions are classified into three
major groups: Electron-withdrawing, electron donating or
combination of both of them [20]. One-Electron Molecular
Orbital (OEMO) theory can explain how these interactions
affect the stability of the single-electron radicals. Based on
the capto-dative concept [21], simultaneous interaction of
the radical centers with the electron-donor and electron-
acceptor substitutions increases the stabilization energy
compared to the sum of their donor- or acceptor-substituted
radicals.
Illustration of the reaction mechanism in Scheme 8 indi-
cates that the elimination of the first proton from each of
THPM(N1)·+ and THPM(N3)·+ intermediates results in the
formation of TrHPM· intermediate. Due to delocalization
of the single electron in this intermediate, the involvement
of two different benzylic/allylic 4 and benzylic/allylic 6
is expected. The experimental results of the present study
revealed that upon irradiation of either 1b or 1e, either 1c
or 1f, and either 1d or 1g, the same products 3b, 3c or 3d
are obtained; therefore, the resultant radicals are respon-
sible to generating of the same photoproducts. Electronic
properties of the substituted aryl ring can affect the sta-
bility of these radicals during the oxidation reaction. The
electron-releasing and electron-accepting properties of the
aryl and phenyl rings can change the HOMO and LUMO
levels on the olefinic C=C double bond, such that electron-
releasing groups increase and electron-accepting groups
decrease these levels of electronic energies, respectively.
Frontier Molecular Orbital (FMO) theory described this
effect [19]. According to this theory, the stability of the
radical species is strongly relay on the nature of substitu-
ents in the α-position. The interaction of the radical center
with the alkyl substituent (via hyper-conjugation), the
Compounds
1b–1d
have
two
aryl
ring
(Ar1 = 4,3,2-(methoxy)-C6H4 and Ar2 = Ph) on the 4- and
6-positions of the heterocyclic ring, respectively. When the
radical species is formed, this radical is benzylic/allylic 4
(Scheme 8). This radical can become benzylic/allylic 6 by
electron delocalization. If this radical existence is on the
4-position, the radical center can interact with the N3 lone
pair as a donor species, the methoxy-substituted aryl ring
again as a donor species and the π or π* orbitals of the
attached C=C double bond. Therefore, an effective capto-
dative stabilization for this radical center is not expected.
In contrast to this situation, when this radical is located on
the 6-position, capto-dative effect is expected due to the
1 3

J IRAN CHEM SOC
simultaneous interaction of the radical center with the N1
lone pair and electron-withdrawing C6 phenyl ring. As a
result, the radical on the 6-position is more stable than on
the 4-position; therefore, the formation of the 4-ph/6-Ar1
product, namely 3b–3d is expected. In the cases of 1e–1g
compounds having the phenyl and the aryl rings (Ar1 = Ph
and Ar2 = 4,3,2-(methoxy)-C6H4) on the 4- and 6-positions
of the heterocyclic ring, respectively, the firstly formed
radical is benzylic/allylic 4. The radical center on this posi-
tion now assigned as a capto-dative stabilized radical and
gained more stability due to the simultaneous interaction
with the N3 lone pair as an electron donor and the phenyl
group as an electron acceptor group, which leads again to
the formation of the 4-ph/6-Ar1 product (3b–3d).
To support the above-mentioned arguments, the benzylic
radical centers on the C4- and C6-positions assigned as part A
and B, respectively. The sum of the Mulliken atomic spin den-
sities of the radicals 1a·, 1b· and 1e· obtained from DFT study
is given in Table 5. The radical 1a· either on the C4-position
(part A) or C6-position (part B) of the heterocyclic ring has
similar benzylic character due to the attachment of the radi-
cal center with the phenyl ring on both positions. Therefore,
the sum of the Mulliken atomic spin densities for both parts is
0.7607. In radical 1b·, the C4-radical center (part A) is attached
to the electron-donating p-methoxyphenyl group, whereas the
C6-radical center (part B) is attached to the electron-withdraw-
ing phenyl ring. The phenyl ring as a part of a capto-dative
radical stabilizes the radical center effectively; therefore,
the sum of the Mulliken spin densities for part B (0.8073)
is greater than for part A (0.7080). The reverse results are
obtained for the radical 1e·, in which the parts A and B contain
the phenyl and p-methoxyphenyl substitutions, respectively;
therefore, the sum of the Mulliken spin densities for part A
(0.7879) is greater than that for part B (0.6969).
Scheme 8 Involvement of two different benzylic/allylic radical inter-
mediates in the oxidative process
Table 5 Sum of the Mulliken spin densities in 1a·, 1b·and 1e· radical intermediates in A and B parts
Sum of the Mulliken spin densities
Part A = ∑ (C4, C9, C11 and C13)
Benzylic/allylic 4 = A
Part B = ∑ (C6, C15, C17 and C19)
Benzylic/allylic 6 = B
1a·
1b·
1e·
0.1352 + 0.1305 + 0.1004 + 0.3946 = 0.7607
0.0974 + 0.1303 + 0.0830 + 0.3973 = 0.7080
0.1478 + 0.1408 + 0.1047 + 0.3946 = 0.7879
0.3946 + 0.1004 + 0.1305 + 0.1352 = 0.7607
0.4039 + 0.1448 + 0.1092 + 0.1494 = 0.8073
0.3922 + 0.1037 + 0.1033 + 0.0977 = 0.6969
1 3

J IRAN CHEM SOC
Table 6 Bond lengths (Å) and dihedral angles (°) of 4,6-diaryl-2-oxo-1,2,3,4-tetrahydropyrimidines (THPMs), trihydropyrimidyl radical
(TrHPM·) obtained by using the B3LYP/6-31++G (d,p) calculations
Comp.
N1–C2
C2–N3
N3–C4
C4–C5
C5–C6
N1–C6
C2–O7
C4–C8
C6–C14 β1
β2
γ1
γ2
1a
1.3889 1.3680 1.4680 1.5093 1.3462 1.4026 1.2290 1.5312 1.4837
1.4347 1.3573 1.4567 1.4885 1.4051 1.3517 1.2127 1.5428 1.4599
1.3823 1.3823 1.4051 1.3932 1.3932 1.4051 1.2248 1.4574 1.4574
1.3876 1.3714 1.4726 1.5125 1.3469 1.4017 1.2289 1.5246 1.4835
1.4235 1.3612 1.4551 1.4924 1.3932 1.3616 1.2152 1.5362 1.4668
1.3813 1.3831 1.4064 1.3908 1.3964 1.4073 1.2254 1.4574 1.4544
1.3878 1.3685 1.4687 1.5094 1.3461 1.4024 1.2295 1.5327 1.4835
1.4221 1.3631 1.4537 1.4988 1.3910 1.3629 1.2155 1.5434 1.4640
1.3816 1.3827 1.4054 1.3923 1.3937 1.4058 1.2252 1.4582 1.4569
1.3952 1.3656 1.4737 1.5049 1.3469 1.4029 1.2291 1.5357 1.4839
1.4403 1.3519 1.4641 1.4782 1.4062 1.3484 1.2127 1.5299 1.4626
1.3856 1.3770 1.4042 1.3975 1.3911 1.4042 1.2264 1.4614 1.4580
1.3874 1.3693 1.4698 1.5090 1.3467 1.4026 1.2294 1.5322 1.4814
1.4260 1.3588 1.4586 1.4912 1.4012 1.3607 1.2149 1.5401 1.4493
1.3828 1.3813 1.4069 1.3964 1.3901 1.4059 1.2253 1.4545 1.4585
1.3867 1.3716 1.4711 1.5115 1.3464 1.4012 1.2288 1.5273 1.4842
1.4359 1.3556 1.4593 1.4869 1.4068 1.3494 1.2128 1.5401 1.4616
1.3822 1.3828 1.4060 1.3941 1.3923 1.4054 1.2250 1.4567 1.4587
1.3896 1.3703 1.4685 1.5116 1.3476 1.4037 1.2295 1.5266 1.4867
1.4287 1.3560 1.4564 1.4888 1.4113 1.3522 1.2149 1.5408 1.4604
1.3769 1.3843 1.4029 1.3900 1.3999 1.4039 1.2266 1.4589 1.4602
−52.1
−43.2
21.2
71.2 −37.5
79.3 −27.4
140.2
1a·+
1a·
1b
1b·+
1b·
1c
149.8
157.4
157.4 −21.1
−54.35
−37.7
−21.3
−51.3
−15.3
−22.8
68.5
67.5
82.9
37.7 −140.8
27.1 −152.9
18.9 −158.0
155.7
72.4 −37.5
105.1 −29.9
155.4 −20.7
140.5
147.2
157.8
1c·+
1c·
1d
−167.3
−156.4
−159.3
38.1 −139.8
27.6 −150.6
21.4 −156.6
1d·+
1d·
1e
1e·+
1e·
74.9
23.5
−56.4
−47.6
−19.7
−53.9
−50.6
−20.2
−54.0
−49.2
−21.7
67.4 −37.8
73.2 −22.1
140.5
155.0
155.2
158.7 −23.5
1f
67.9
73.2
38.6 −139.7
27.1 −151.8
21.6 −155.3
44.6 −138.4
1f·+
1f·
156.8
67.6
1 g
1g·+
1g·
74.6 −10.9
167.6
155.5
19.8 −161.4
β1 = N3–C4–C8–C9 dihedral angle; β2 = C4–C5–C8–C9 dihedral angle; γ1 = N1–C6–C14–C15 dihedral angle; γ1 = C5–C6–C14–C15 dihedral angle
The results of the DFT study from the optimized struc-
tures for the selected bond lengths and inner-ring and inter-
ring dihedral angles are extracted and listed in Table 6.
Comparison of the bond lengths of each compound and its
corresponding radical cation intermediate indicates that the
first electron removal occurred from the N1-atom, which
displays on the drastic shortening of the N1–C6 bond length,
while comparison of the bond lengths of each compound
and its corresponding radical intermediate indicates that the
effective benzylic stabilization by the phenyl ring is char-
acterized by comparatively shorter C4–Cphenyl or C6–Cphenyl
bond lengths with the C6–Caryl or C4–Caryl bond lengths.
radical centers and Mulliken population analysis support
the results of the experimental work.
Experimental
5-Unsubstituted
4,6-diaryl-2-oxo-1,2,3,4-tetrahydropy-
rimidines (THPMs) considered in the present work were
synthesized by the reported procedure [22]. All irradia-
tions were performed using a 400 W high-pressure Hg-
vapor lamp from NARVA. The cyclic voltammetry (CV)
measurements were performed using SAMA 500 Poten-
tio/Galvanostat. All electrochemical experiments were
carried out in a conventional three-electrode system at
room temperature. A silver electrode, a large area Pt plate
(99.99%) and a glass carbon electrode (GCE) were used
as reference, counter and working electrodes, respectively.
Conclusion
In summary, this present work describes electron-trans-
fer-induced photo-oxidation of various 4,6-diaryl-2-oxo-
1,2,3,4-tetrahydropyrimidines (THPMs) to 4,6-diaryl-
2-oxo-3,4-dihydropyrimidines in chloroform solvent under
argon atmosphere. The results indicate that the capto-
dative stabilized radical intermediate between two pos-
sibly formed double benzylic/allylic radical centers con-
trolled the type of formed product. The data of the DFT
computational studies concerning the bond lengths to the
General procedure for Photo‑oxidation
of 4,6‑diaryl‑2‑oxo‑1,2,3,4‑tetrahydropyrimidines
(THPMs)
A solution of 5-unsubstituted 4,6-diaryl-2-oxo-1,2,3,4-
tetrahydropyrimidines (0.04 mmol) in 10 ml of distilled
1 3

J IRAN CHEM SOC
10. H.R. Memarian, A. Farhadi, H. Sabzyan, M. Soleymani, J. Pho-
tochem. Photobiol. A: Chem. 209, 95 (2010)
11. H.R. Memarian, A. Farhadi, Monatsh. Chem. 140, 1217 (2009)
12. H.R. Memarian, M. Soleymani, H. Sabzyan, J. Iran. Chem. Soc.
9, 805 (2012)
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16. H.R. Memarian, M. Soleymani, Ultrason. Sonochem. 18, 745
(2011)
chloroform (c = 4 mM) was irradiated under bubbling of
argon gas with a 400-W high-pressure mercury lamp in
a Pyrex tube at ambient temperature. The progress of the
reaction was monitored by TLC until total disappearance of
starting material. After completion of reaction, the solvent
was evaporated to obtain the pure product. The physical
and spectroscopic data of the product are already reported
[23].
17. H.R. Memarian, M. Ranjbar, H. Sabzyan, A. Kiani, C. R.
Chimie. 15, 1001 (2012)
Acknowledgements We are thankful to the Research Council and
Office of the Graduate Studies of the University of Isfahan for finan-
cial supports.
18. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A.
Robb, J.R. Cheeseman, V.G. Zakrzewski, J.A. Montgomery,
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