Oxidation studies on some natural monoterpenes: Citral, pulegone, and camphene

Article abstract of DOI:10.1134/S1070428008060067

Citral extracted from Cymbopogon citratus (Gramineae) was subjected to photochemical epoxidation with hydrogen peroxide to obtain a mixture of epoxy derivatives at the C²=C³ and C⁶=C⁷ double bonds. The thermal oxidation of citral with m-chloroperoxybenzoic acid at room temperature gave only the corresponding 6,7-epoxy derivative as a mixture of E and Z isomers with respect to the C²=C³ double bond. Photosensitized oxygenation of citral in the presence of tetraphenylporphyrin, Rose Bengal, or chlorophyll lead to a mixture of two isomeric hydroperoxides, (2E)-6-hydroperoxy-3,7-dimethylocta-2,7-dienal and (2E,5E)-7-hydroperoxy-3,7- dimethylocta-2,5-dienal. Epoxidation of pulegone isolated from Penny royal oil (Mentha pulegium, Lamiaceae) with hydrogen peroxide under irradiation with a sodium lamp lead to a mixture of cis- and trans-isomeric 2,2,6-trimethyl-1- oxaspiro[2.5]octan-4-ones, whereas under conditions of photosensitized oxygenation two hydroperoxide derivatives, 2-(1-hydroperoxy-1-methylethyl)-5- methylcyclohex-2-en-1-one and 2-hydroperoxy-5-methyl-2-(1-methylethenyl) cyclohexan-1-one, were also formed. Camphene reacted with hydrogen peroxide under irradiation to give a mixture of the corresponding endo- and exo-epoxy derivatives and camphor, while its thermal oxidation with m-chloroperoxybenzoic produced only the two former.

Full text of DOI:10.1134/S1070428008060067

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 6, pp. 814–822. © Pleiades Publishing, Ltd., 2008.
Published in Russian in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 6, pp. 825–833.
Oxidation Studies on Some Natural Monoterpenes:
Citral, Pulegone, and Camphene*
a
b
E. M. Elgendy and S. A. Khayyat
a
Faculty of Specific Education, Mansoura University, Mansoura, Egypt
e-mail: eman_elgendy@hotmail.com
b
Faculty of Educational’s Girls, Ministry of Education, Jeddah, Saudi Arabia
Received September 30, 2006
Abstract—Citral extracted from Cymbopogon citratus (Gramineae) was subjected to photochemical epoxida-
2
3
6
7
tion with hydrogen peroxide to obtain a mixture of epoxy derivatives at the C =C and C =C double bonds.
The thermal oxidation of citral with m-chloroperoxybenzoic acid at room temperature gave only the corre-
2
3
sponding 6,7-epoxy derivative as a mixture of E and Z isomers with respect to the C =C double bond. Photo-
sensitized oxygenation of citral in the presence of tetraphenylporphyrin, Rose Bengal, or chlorophyll lead to
a mixture of two isomeric hydroperoxides, (2E)-6-hydroperoxy-3,7-dimethylocta-2,7-dienal and (2E,5E)-7-hy-
droperoxy-3,7-dimethylocta-2,5-dienal. Epoxidation of pulegone isolated from Penny royal oil (Mentha
pulegium, Lamiaceae) with hydrogen peroxide under irradiation with a sodium lamp lead to a mixture of cis-
and trans-isomeric 2,2,6-trimethyl-1-oxaspiro[2.5]octan-4-ones, whereas under conditions of photosensitized
oxygenation two hydroperoxide derivatives, 2-(1-hydroperoxy-1-methylethyl)-5-methylcyclohex-2-en-1-one
and 2-hydroperoxy-5-methyl-2-(1-methylethenyl)cyclohexan-1-one, were also formed. Camphene reacted with
hydrogen peroxide under irradiation to give a mixture of the corresponding endo- and exo-epoxy derivatives
and camphor, while its thermal oxidation with m-chloroperoxybenzoic produced only the two former.
DOI: 10.1134/S1070428008060067
Natural monoterpenes, citral (I), pulegone (II), and
camphene (III) were found in a wide variety of plants
exposure to air. Oxidation is enhanced by heat [6],
irradiation [7], or chemical catalysts [8]. The oxidation
process can also be initiated by attack of reactive
singlet oxygen, as in photooxidation. Photooxidation
provides an important way to produce hydroperoxides
in the presence of oxygen, light energy, and photo-
sensitizers [9]. Photosensitizers absorb visible or near-
UV light to become electronically excited. Sensitizer
[1]; these compounds are non-nutrient dietary com-
ponents of fruits and essential oils of citrus fruits,
cherries, spearmint dill, caraway, apricots, and grapes.
The most investigated monoterpenes are limonene,
carvone, carveol, and perillyl alcohol, especially from
the viewpoint of their chemotherapeutic activity [2].
in the triplet state reacts with oxygen through energy
1
OH
transfer to give singlet oxygen ( O ); the latter is
2
Me
Me
Me
highly electrophilic, and it reacts rapidly with double
bonds of monoterpenes according to the ene mechan-
ism. As a result, unstable neutral primary oxidation
products such as hydroperoxides are formed. Hydro-
peroxides may give rise to secondary oxidation prod-
ucts having multiple chemical functional groups (hy-
droxy, oxo, and epoxy derivatives) [10]. Furthermore,
unsaturated terpenes are capable of trapping activated
oxygen species in vivo to give intermediate epoxides
and hydroperoxides, which can alkylate or damage
DNAs, proteins, and other biomolecules [6, 11].
O
HO
H C
Me
H C
Me
H C
Me
H C
Me
2
2
2
2
Limonene
Perillyl alcohol
Carvone
Carveol
A number of dietary monoterpenes were shown to
act effectively in chemoprevention and chemotherapy
of different cancers in animal models, at cellular level,
and in human clinical trials [3–5]. On the other hand,
plant monoterpenes are subjected to oxidation on
It is well known that some monoterpenes undergo
oxidation by the action of hydrogen peroxide under
thermal conditions to give the corresponding epoxy
*
The text was submitted by the authors in English.
8
14

OXIDATION STUDIES ON SOME NATURAL MONOTERPENES:
815
derivatives [12, 13]; however, no attention was given
to the preparation of such epoxides via photochemical
oxidation reactions. Taking into account therapeutic
importance of monoterpene compounds, we believed it
to be relevant to examine some oxidation reactions of
citral (I), pulegone (II), and camphene (III).
ratio of the signals at δ 5.85 and 5.93 ppm being
36:64. Isomers Ia and Ia′ were characterized by dif-
ferent retention times, 18.231 and 18.183 min, respec-
tively (62 and 38%), and by the same m/z value (168)
for the molecular ion (GC–MS data). Compound Ib
1
displayed in the H NMR spectrum singlets at δ 1.62
and 1.70 ppm from protons in the two methyl groups at
the double bond and a doublet at δ 10.0 ppm from the
aldehyde proton. The molecular ion of Ib had an m/z
value of 168.
Citral [I, (2E,Z)-3,7-dimethylocta-2,6-dienal] is
a monoterpene aldehyde which is the major component
of lemon grass oil extracted from Cymbopogon citra-
tus belonging to Gramineae [14–16] as a mixture of
(
2E)- and (2Z)-isomers at a ratio of 3:2 respectively.
By oxidation of citral (I) with m-choroperoxy-
benzoic acid in chloroform at room temperature we
obtained a mixture of E- and Z-epoxides Ia and Ia′ at
a ratio of 60 :40 in an overall yield of about 60%,
while no other products were detected (Scheme 1).
Interestingly, the photooxygenation of compound I in
the presence of tetraphenylporphyrin (TPP), Rose
Bengal (RB), or chlorophyll (CP) as singlet oxygen
sensitizer gave a mixture of (2E,5E)-7-hydroperoxy-
3,7-dimethylocta-2,5-dienal (Ic) and (2E)-6-hydro-
peroxy-3,7-dimethylocta-2,7-dienal (Id) (Scheme 1) in
an overall yield of 25.5, 11.5, and 15.6%, respectively,
the ratio Ic:Id being 60:40 in all cases (according to
1
The H NMR spectrum of (I) contains two doublets at
δ 9.98 and 9.87 ppm with an intensity ratio of 3:2
from the aldehyde proton in the E and Z isomer,
respectively. Photochemical epoxidation of citral (I)
with 30% hydrogen peroxide in ethanol using a sodium
lamp gave a mixture of (2E,Z)-5-(3,3-dimethyloxiran-
2
-yl)-3-methylpent-2-enal (Ia/Ia′) and 3-methyl-3-
[
(
(3E)-4-methylpent-3-en-1-yl)oxirane-2-carbaldehyde
Ib) in 21.5 and 11.5% yield, respectively (Scheme 1).
The structure of compounds Ia/Ia′ and Ib was deter-
mined on the basis of spectral measurements. The
1
1
H– H COSY spectrum of Ia/Ia′ showed two upfield
1
singlets at δ 1.27 and 1.32 ppm due to methyl groups
on the oxirane ring, and a multiplet at δ 2.30 ppm from
the methylene protons in position 4; doublets at δ 5.85
and 9.97 ppm were assigned to the olefinic proton in
position 2 and aldehyde proton, respectively, of the Z
isomer (Ia′), while multiplet signal at δ 5.93 ppm and
doublet at δ 9.99 ppm were attributed to the corre-
sponding protons in the E isomer (Ia), the intensity
the H NMR data). The yield depended on the sen-
sitizer activity, and it decreased in going from TPP to
CP and then to RB. We succeeded in isolating by
column chromatography only the major component,
hydroperoxide Ic, as individual substance. The struc-
ture of products Ic and Id was confirmed by spectral
1
1
data. Hydroperoxide Ic displayed in the H– H NMR
COSY spectrum a multiplet at δ 5.65 ppm and a dou-
Scheme 1.
Me
Me
CHO
CHO
H O , hν
O
2
2
+
O
1
0
Me
Me
Me
Me
Me
Ib
1
3
Ia/Ia'
CHO
4
5
2
3
-ClC H CO H
6 4 3
Ia/Ia'
6
7
9
8
Me
Me
Me
Me
I
CHO
CHO
OOH
1
O , hν
2
+
OOH
Me
Me
Me
CH2
Id
Ic
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008

8
16
ELGENDY, KHAYYAT
Scheme 2.
Me
Me
CHO
CHO
H
O
–
ROH
O
Me
OR
CHO
Me
Me
Me
Me
ROOH, hν
A
Ia/Ia'
Me
Me
CHO
Me
Me
CHO
I
O
H
OH
–H O
2
Me
Me
Me
Me
Ib
B
6 4
R = H, 3-ClC H CO.
blet at 5.72 ppm from the olefinic protons in positions
and 6, respectively, and a singlet at δ 8.10 from the
ination of water or m-chlorobenzoic acid molecule,
depending on the oxidant used, gives the final products
(Scheme 2). In the photosensitized oxidation of citral
(I), hydroperoxides Ic and Id are likely to be formed
through peroxirane intermediate C which is stabilized
along two possible pathways a and b (Scheme 3).
5
1
OOH proton. The H NMR spectrum of Id contained
a broadened singlet at δ 4.93 ppm from the 6-H proton
and a singlet at δ 8.05 from the OOH proton. Com-
pounds Ic and Id showed in the mass spectra the
molecular ion peak with m/z 184.
Analogous oxidation reactions were performed with
another natural monoterpene, pulegone (II, 2-iso-
propylidene-5-methylcyclohexan-1-one) which is the
major component of Penny royal oil. Compound II
was isolated by extraction of Mentha pulegium (Lami-
It is believed that citral (I) is oxidized with H O in
2
2
a thermal reaction. This behavior was studied previ-
ously by Yarovaya et al. [12] who reported that the
epoxidation of I with hydrogen peroxide in acidic
medium gave compounds Ia and Ia′ and that in basic
medium only epoxide Ib was formed as a mixture of
cis and trans isomers. A probable mechanism for the
formation of epoxy derivatives Ia, Ia′, and Ib is be-
lieved to involve oxirane intermediates A and B; elim-
1
aceae) leaves [17–20]. In the H NMR spectrum of II,
a doublet at δ 1.01 ppm due to 5-CH group and two
3
singlets at δ 1.78 and 1.98 ppm due to isopropylidene
group were present. Photochemical epoxidation of
pulegone (II) with 30% hydrogen peroxide in ethanol
Scheme 3.
Me
CHO
a
Me
Me
OOH
Me
Ic
CHO
CHO
Me
1
O , hν
2
a
b
H a
Me
O
O
b
CHO
OOH
Me
Me
H
Me
I
C
b
Me
CH2
Id
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008

OXIDATION STUDIES ON SOME NATURAL MONOTERPENES:
817
Scheme 4.
Me
H O , hν
2
2
O
Me
7
Me
O
5
Me
IIa/IIa'
4
3
6
1
2
O
Me
Me
1
0
9
8
Me
Me
1
O , hν
2
II
IIa/IIa'
+
+
O
O
HOO
H C
Me
Me
OOH
Me
2
IIb
IIc
under irradiation with a sodium lamp gave a mixture of
,2,6-trimethyl-1-oxaspiro[2.5]octan-4-ones IIa and
IIa′ with different mutual orientations of the oxirane
ring and 7-methyl group with respect to the cyclo-
hexane ring; the overall yield of IIa/IIa′ was about
formation of the above epoxides IIa and IIa′, 2-(1-hy-
droperoxy-1-methylethyl)-5-methylcyclohex-2-en-1-
one (IIb), and 2-hydroperoxy-2-isopropenyl-5-methyl-
cyclohexan-1-one (IIc). Compounds IIb and IIc were
isolated as individual substances; the yields are given
in table (Scheme 4). The structure of IIb and IIc was
2
4
0%, and their ratio was 45 : 55 (Scheme 4). The
1
1
H NMR spectrum contained doublets at δ 1.06 ppm
confirmed by spectral data. The H NMR spectrum of
7
(
J = 7 Hz) from the axial methyl group on C (α-iso-
IIb contained two singlets at δ 1.38 and 1.46 ppm from
the side-chain isopropyl fragment, a doublet of dou-
blets at δ 5.51 ppm (J = 3, 3.6 Hz) from the olefinic
proton in position 3 of the cyclohexene ring, and
a singlet at 8.8 ppm from the OOH group. Compound
IIb was characterized by a retention time of
mer IIa) and at δ 1.09 ppm (J = 6 Hz) from the
equatorial 7-methyl group (β-epoxide IIa′). Also, two
singlets at δ 1.22 and 1.23 ppm were observed due to
1
0
methyl groups on C in isomers IIa and IIa′, respec-
tively. According to the GC–MS data, the molecular
ions of IIa and IIa′ have an m/z value of 168, and their
retention times are 10.85 and 11.05 min, respectively
1
6.626 min (GC–MS), and its mass spectrum contain-
ed the molecular ion peak with m/z 184. Hydroper-
1
(
GC peak area ratio 45:55).
oxide IIc displayed in the H NMR spectrum a doublet
7
Photosensitized reaction of II with singlet oxygen
in the presence of tetraphenylporphyrin (TPP), Rose
Bengal (RB), and chlorophyll (CP) resulted in the
at δ 1.0 ppm and a singlet at δ 1.8 ppm from the C H
3
8
and C H
methyl groups, and the hydroperoxide proton
3
resonated as a singlet at δ 9.85 ppm. The retention time
Photosensitized oxygenation of citral (I) and pulegone (II) in the presence of tetraphenylporphyrin, Rose Bengal, and
chlorophyll
Initial
comp. no.
a
b
Solvent
Sensitizer
Reaction time, h
Overall yield, %
Products (ratio )
I
CHCl
EtOH
CHCl
CHCl
EtOH
CHCl
3
TPP
RB
CP
7.0
7.5
7.0
5.5
8.0
7.0
25.5
11.5
15.6
50.0
33.0
40.0
Ic, Id (60:40)
I
Ic, Id (60:40)
I
3
3
Ic, Id (60:40)
II
II
II
TPP
RB
CP
IIa/IIa′, IIb, IIc (30:38.5:31.5)
IIa/IIa′, IIb, IIc (18:45:37)
IIa/IIa′, IIb, IIc (25:41:34)
3
a
TPP stands for tetraphenylporphyrin, RB stands for Rose Bengal, and CP stands for chlorophyll.
The product ratios were calculated from the H NMR spectrum of the reaction mixture.
b
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008

8
18
ELGENDY, KHAYYAT
Scheme 5.
O
O
O
Me
H
O
Me
O
O
Me
Me
HOOH
Me
O
+
HO
Me
–
H O
2
Me
Me
Me
IIa
Me
Me
Me
II
D
IIa'
of IIc was 19.053 min (GC–MS), and its molecular ion
had the same m/z value as that of IIb.
ethanol, sodium lamp) and obtained a mixture of endo-
and exo-isomers of 3,3-dimethylspiro[bicyclo[2.2.1]-
heptane-2,2′-oxirane] (IIIa/IIIa′) in ~25% yield (ratio
Ngo et. al. [21] successfully prepared α- and β-ep-
oxides IIa and IIa′ at a ratio of 1:1 by oxidation of
pulegone (II) with m-chloroperoxybenzoic acid at
room temperature. A probable mechanism of forma-
tion of compounds IIa and IIa′ is shown in Scheme 5.
Addition of H O at the exocyclic double bond can
2
:1) and camphor (IIIb) in ~15% yield (Scheme 7).
The oxidation of III with m-chloroperoxybenzoic acid
in chloroform at room temperature gave 75% of epox-
ides IIIa/IIIa′ (Scheme 7). Methylene protons in the
1
oxirane ring IIIa/IIIa′ appeared in the H NMR spec-
2
2
trum of the isomer mixture as two doublets for each
isomer at δ 2.67/2.69 (IIIa) and 2.75/2.78 ppm (IIIa′).
occur at both sides with respect to the cyclohexane
ring; intermediate oxirane then loses H O molecule to
2
7
The molecular ions of IIIa/IIIa′ had an m/z value of
give two isomeric products. The methyl group on C
1
1
52. The H NMR spectrum of IIIb was consistent
and the oxirane oxygen atom are arranged trans with
respect to each other in isomer IIa and cis in IIa′.
with the spectrum of an authentic sample of camphor,
which showed the absence of exocyclic methylene
protons. The IR spectrum of IIIb contained a carbonyl
Me
O
Me
Me
Me
–
1
absorption band at 1704 cm .
O
The formation of camphor (IIIb) in the photo-
chemical epoxidation of camphene (III) with hydrogen
peroxide seems to be unusual. Presumably, compound
IIIb arises from photoinitiated rearrangement of III,
followed by hydrogen peroxide attack as shown in
O
Me
Me
IIa
IIa'
Photosensitized oxygenation of pulegone (II) is
likely to involve peroxirane transition state D which
is stabilized according to pathway a or b, yielding
(
Scheme 8). Yarovaya et al [13] reported that epoxida-
tion of III with hydrogen peroxide under thermal
conditions gave epoxy derivatives IIIa and IIIa′ at
a ratio of 2.3:1. We have found no published data on
photochemical epoxidation of camphene (III).
It is known that some hydroperoxides cause photo-
chemical DNA damage [22, 23]. Therefore, compounds
Ic and IIb were tested for DNA-damaging activity.
For this purpose, a sample of DNA in saline was
2
2
-(1-hydroperoxy-1-methylethyl)-5-methylcyclohex-
-en-1-one (IIb) and 2-hydroperoxy-2-isopropenyl-5-
methylcyclohexan-1-one (IIc), respectively (Scheme 6),
together with cis- and trans-epoxides IIa′ and IIa.
We also performed epoxidation of camphene (III)
under analogous conditions (30% hydrogen peroxide,
Scheme 6.
O
Me
Me
Me
O
O
a
b
a
OOH
O
Me
1O2
Meb
Me
IIb
a
Me
O
b
a
H
b
O
Me
Me
H
Me
II
E
H C
2
OOH
IIc
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008

OXIDATION STUDIES ON SOME NATURAL MONOTERPENES:
819
Scheme 7.
8
Me
9
1
4
Me 1
Me
1
0
10
O
H O , hν
6
5
Me6
2
2
2
3
2
3
7
+
7
9
8
Me 5
Me
Me
O
4
IIIa/IIIa'
IIIb
CH2
3
-ClC H CO H
6
4
3
III
IIIa/IIIa'
Scheme 8.
Me
Me
Me
Me
Me
Me
HOOH, hν
+
O
O
Me
Me
H
O
IIIa
IIIa'
OH
Me
CH2
III
Me
Me
hν
Me
H
2
O
2
Me
Me
·
·
·
·
H
CH2
·
CH2
·
O
OH
H
Me
Me
Me
Me
H
–H
2
O
O
O
OH
Me
Me
IIIb
mixed with a solution of hydroperoxide Ic or IIb in
ethanol, and the mixture was irradiated using a sodium
lamp. The results (see Experimental) clearly indicated
moderate and high degrees of DNA degradation in the
presence of compounds Ic and IIb, respectively, when
the irradiation time was prolonged to 8 h.
a Joel JMS 600H mass spectrometer coupled with
a Hewlett–Packard HP 6890 Series gas chromatograph
(HP-5 capillary column, 30 m×0.32 mm×0.25 μm;
cross linked 5% dimethylpolysiloxane). A Philips
G/5812 SON sodium lamp was used as irradiation
source in photoinitiated reactions. Thin-layer chroma-
tography (TLC) and preparative thin-layer chromatog-
raphy were performed using Polygram SIL G/W 254
silica gel (Mecherey-Nagel). Solvents were removed
from reaction mixtures and extracts using a rotary
evaporator (20°C, 15 mm).
EXPERIMENTAL
Citral (I) and pulegone (II) were isolated by extrac-
tion of Cymbopogon citratus and Manthu pulegium
plants, respectively, which were collected from
Maddinah city (Saudi Arabia). Camphene (III) was
supplied by Sigma Chemical Co. The melting points
Citral [I, (2E,Z)-3,7-dimethylocta-2,6-dienal].
Colorless oil, C H O (M 152.238). IR spectrum, ν,
1
0
16
–
1
1
cm : 2971, 2924, 1675, 1636, 1122. H NMR spec-
trum, δ, ppm: E isomer: 1.58 s (3H, C H ), 1.67 s (3H,
9
(
uncorrected) were determined on a Fisher electric
3
8
10
melting point apparatus. The IR spectra were recorded
on a Perkin–Elmer 16 FPC FT-IR spectrophotometer
from thin films (neat). The NMR spectra were meas-
C H ), 2.17 s (3H, C H ), 2.23 m (2H, 5-H), 2.59 d.d
3 3
(2H, 4-H, J = 8 Hz), 5.08 m (1H, 6-H), 5.86 d (1H,
2-H, J = 8 Hz), 9.98 d (1H, CHO, J = 8 Hz); Z isomer:
1
0
ured from solutions in CDCl on a Bruker Avance
1.99 s (3H, C H ), 9.87 d (1H, CHO, J = 8 Hz); the
3
3
1
DPX 400 instrument (400 MHz for H). Gas chroma-
other signals are the same as for the E isomer.
1
3
9
tography–mass spectrometry was performed using
C NMR spectrum, δ , ppm: E isomer: 17.65 (C ),
C
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008

8
2
(
(
20
ELGENDY, KHAYYAT
1
0
5
8
4
+
+
+
5.71 (C ), 27.01 (C ), 32.55 (C ), 40.58 (C ), 127.38
[C H ] , 81 (100) [C H ] , 71 (5) [C H O] , 41 (60)
7
11
6
9
4
7
6
2
7
3
+
C ), 128.62 (C ), 132.87 (C ), 133.65 (C ), 163.88
[C H ] .
3 5
1
10
2
1
C ); Z isomer: 25 (C ), 122.55 (C ), 163.85 (C ); the
other signals are the same as for the E isomer.
3
-Methyl-3-(4-methylpent-3-en-1-yl)oxirane-2-
carbaldehyde (Ib). Colorless oil, C H O
2
M 168.238). IR spectrum, ν, cm : 2987, 2933, 1715,
1645, 1149. H NMR spectrum 1.23 s (3H, C H ),
.30 m (2H, 4-H), 1.62 s (3H, C H ), 1.70 s (3H,
3
1
0
16
–
1
Pulegone (II, 2-isopropylidene-5-methylcyclo-
hexan-1-one). Colorless oil, C H O (M 152.238). IR
spectrum, ν, cm : 2922, 1677, 1613, 1445, 1122.
H NMR spectrum, δ, ppm: 1.01 d (3H, C H , J =
(
1
10
1
0
16
3
–
1
8
1
1
7
9
3
C H ), 2.15 m (2H, 5-H), 3.85 m (1H, 6-H), 5.10 br.s
(1H, 2-H), 10.0 d (1H, CHO). GC–MS data: retention
3
8
7
(
(
(
Hz) 1.34 m (2H, 4-H), 1.78 s (3H, C H ), 1.87 m
3
9
+
1H, 5-H), 1.98 s (3H, C H ), 2.02 t (1H, 3-H), 2.26 t
1H, 3-H), 2.50 d.d (1H, 6-H, J = 16, 2 Hz), 2.72 d.d
1H, 6-H, J = 16, 5 Hz). C NMR spectrum, δ , ppm:
1.5 (C ), 22 (C ), 23 (C ), 28.5 (C ), 31.5 (C ), 33
3
time 10.333 min; m/z (I , %): 168 (1) [M] , 152 (15)
rel
+
+
+
[
(
(
M – O] , 137 (20) [M – CH O] , 125 (5) [C H ] , 123
3 9 17
1
3
+
+
+
C
5) [C H ] , 95 (40) [C H ] , 82 (100) [C H ] , 55
9
15
7
11
6
10
8
9
7
3
5
2
+
+
15) [C H ] , 41 (60) [C H ] .
4
7
3
5
4
6
10
2
1
(
C ), 51 (C ), 132 (C ), 142 (C ), 200 (C ).
2
,2,6-Trimethyl-1-oxaspiro[2.5]octan-4-one
Photochemical epoxidation of natural terpenes
(
IIa/IIa′). Colorless oil, C H O (M 168.238). IR
1
0
16
2
I–III with hydrogen peroxide (general procedure).
A 30% solution of hydrogen peroxide, 2.5 ml, was
carefully added dropwise over a period of 5 min to
a solution of 5 mmol of compound I–III in 25 ml of
ethanol under stirring at 0°C. The mixture was irra-
diated with a sodium lamp for 55 h (in the reactions
with I and II) or 21 h (in the reaction with III) under
nitrogen. The mixture was then evaporated under
reduced pressure at room temperature, the gummy
residue was treated with 25 ml of chloroform, and the
extract was dried over anhydrous sodium sulfate and
evaporated under reduced pressure. The residue was
subjected to column chromatography on silica gel
using petroleum ether (bp 60–80°C)–diethyl ether
–1
spectrum, ν, cm : 2960, 2868, 1721, 1568, 1460,
1
1
1
116, 1102. H NMR spectrum, δ, ppm: α-isomer IIa:
7
8
.06 d (3H, C H , J = 7 Hz), 1.22 s (3H, C H ), 1.44 s
3
3
9
(
3H, C H ), 1.86 m (1H, 5-H), 2.00 m (2H, 4-H),
3
2
.18 d.d.d (1H, 3-H), 2.46 m (2H, 3-H, 6-H), 2.6 d
7
(
1H, 6-H); β-isomer IIa′: 1.09 d (3H, C H , J = 6 Hz),
3
8
1
.23 s (3H, C H ); the other signals were the same as
3
1
3
for isomer IIa. C NMR spectrum, δ , ppm: α-isomer
C
7
8
9
3
IIa: 18.6 (C H ), 19.3 (C H ), 19.6 (C H ), 21.7 (C ),
3
3
3
5
4
6
10
2
2
2
1
5
9.7 (C ), 32.7 (C ), 42.7 (C ), 49.2 (C ), 63.2 (C ),
7
8
06.3 (CO); β-isomer IIa′: 19.1 (C H ), 19.4 (C H ),
3
3
9
3
5
4
6
9.6 (C H ), 26.0 (C ), 30.4 (C ), 33.7 (C ), 42.7(C ),
3
10
2
1.1 (C ), 70.0 (C ), 207.4 (CO). GC–MS data: reten-
tion time, min: 10.85 (IIa), 11.05 (IIa′); m/z (I , %):
α-isomer IIa: 168 (25) [M] , 153 (80) [M – CH ] , 125
rel
(
9:2) as eluent to isolate: from I: 0.18 g of isomer
+
+
3
mixture Ia/Ia′ and 0.10 g of compound Ib, ratio
Ia/Ia′:Ib = 64:36, overall yield 33%; from II: 0.34 g
of isomer mixture IIa/IIa′, yield 40%; from III: 0.19 g
of isomer mixture IIIa/IIIa′ and 0.11 g of IIIb, ratio
IIIa/IIIa′:IIIb = 63:37, overall yield 40%.
+
+
(
20) [C H O ], 123 (5) [C H O ] , 111 (50) [C H O ] ,
7 9 2 7 7 2 6 7 2
+
+
9
7 (10) [C H ] , 86 (35) [C H O ], 70 (30) [C H O] ,
7 13 4 6 2 4 6
+
+
4
3 (100) [C H ] ; β-isomer IIa′: 168 (5) [M] , 153 (80)
3
7
+
+
+
[
M – CH ], 135 (10) [M – H O], 125 (5) [(C H O ] ,
3 2 7 9 2
+
+
+
1
5
11 (10) [C H O ] , 97 (35) [C H ] , 86 (5) [C H O ] ,
6 7 2 7 13 4 6 2
5 (20) [C H ] , 43 (100) [C H ] .
(
2E,Z)-5-(3,3-Dimethyloxiran-2-yl)-3-methylpent-
-enal (Ia/Ia′). Colorless oil, C H O (M 168.238).
IR spectrum, ν, cm : 2965, 2906, 1720, 1666, 1445,
+
+
4
7
3
7
2
10
16
2
–
1
Oxidation of citral (I) and camphene (III) with
1
1
1
m-chloroperoxybenzoic acid. A solution of 10 mmol
of 80% m-chloroperoxybenzoic acid was carefully
added in a dropwise manner over a period of 15 min to
a solution of 5 mmol of compound I or III in 25 ml of
chloroform at 0°C, and the mixture was stirred at room
temperature under nitrogen, the progress of the reac-
tion being monitored by TLC and peroxide test with
a 10% solution of KI. The mixture was then carefully
1
375, 1160. H NMR spectrum ( H– H COSY), δ,
ppm: E isomer Ia: 1.27 s (3H, C H ), 1.32 s (3H,
C H ), 1.67 s (3H, C H ), 1.77 m (2H, 5-H), 2.3 m
2H, 4-H), 2.76 m (1H, 6-H). 5.93 d (1H, 2-H, J =
Hz), 9.99 d (1H, CHO, J = 8 Hz; Z isomer Ia′: 1.6 s
9
3
8
10
3
3
(
8
(
1
0
3H, C H ), 5.85 d (1H, 2-H, J = 8 Hz), 9.97 d (1H,
CHO, J = 8 Hz); the other signals were the same as for
3
Ia. GC–MS data: retention time, min: 18.231 (Ia),
+
1
(
9
4
8.183 (Ia′); m/z (I , %): isomer Ia: 168 (6) [M] , 153
washed with a saturated aqueous solution of NaHCO
(3×10 ml) and distilled water (3×10 ml). The organic
layer was separated, dried over anhydrous Na SO , and
3
rel
+
+
+
15) [M – CH ] , 137 (2) [M – CH O] , 123 (5) [C H ] ,
3 3 9 15
+
+
+
5 (30) [C H ] , 81 (100) [C H ] , 71 (25) [C H O] ,
2
4
7
11
6
9
4
7
+
+
1 (50) [C H ] ; isomer Ia′: 168 (3) [M] , 152 (3) [M –
O] , 137 (10) [M – CH O] , 123 (15) [C H ] , 95 (40)
evaporated under reduced pressure at room tempera-
ture, and the residue was subjected to column chroma-
3
5
+
+
+
3
9
15
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008

OXIDATION STUDIES ON SOME NATURAL MONOTERPENES:
821
tography on silica gel using petroleum ether (bp 60–
0°C)–diethyl ether (9:2) as eluent to isolate 0.5 g
(2E,5E)-7-Hydroperoxy-3,7-dimethylocta-2,5-di-
enal (Ic). Colorless oil, C H O (M 184.238). IR
8
1
0
16
3
–
1
(
(
60%) of isomer mixture Ia/Ia′ (from I) or 0.57 g
75%) of isomer mixture IIIa/IIIa′ as a viscous oil.
spectrum, ν, cm : 3423, 2965, 2863, 1715, 1620,
1
1456, 1138. H NMR spectrum, δ, ppm: 1.34 s (6H,
8
9
10
C H , C H ), 2.21 s (3H, C H ), 2.95 d (2H, 4-H, J =
3
,3-Dimethylspiro[bicyclo[2.2.1]heptane-2,2′-ox-
3
3
3
6
Hz), 5.65 m (1H, 5-H), 5.72 d (1H, 6-H, J = 12 Hz),
irane] (IIIa/IIIa′). Colorless oil, C H O (M 152.238).
1
0
16
–
1
IR spectrum, ν, cm : 2966, 2868, 1649, 1465, 1347,
5.90 d (1H, 2-H, J =8 Hz), 8.10 s (1H, OOH), 9.96 d
(1H, CHO, J = 8 Hz). GC–MS data: retention time
1
1
0
7
100. H NMR spectrum, δ, ppm: endo isomer IIIa:
9
10
+
.8 s (3H, C H ), 0.89 s (3H, C H ), 1.13 m (2H,
18.868 min; m/z (Irel, %): 184 (1) [M] , 166 (5) [M –
3
3
+
+
-H), 1.26 d.d (2H, 5-H), 1.37 m (2H, 6-H), 1.86 m
H
2
O] , 151 (25) [M – HO
2
] , 123 (30) [C
9
H
15], 108
+
+
+
(
1H, 1-H), 1.96 br.s (1H, 4-H), 2.67 d (1H, 8-H, J =
(80) [C H ] , 91 (35) [C H ] , 79 (100) [C H O] , 43
(50) [C H ] , 39 (40) [C H ] .
8
12
7
7
5
3
+
+
4
0
7
Hz), 2.69 d (1H, 8-H, J = 4 Hz); exo isomer IIIa′:
3
7
3
3
9
10
.81 s (3H, C H ), 0.90 s (3H, C H ), 1.17 m (2H,
3
3
(
2E)-6-Hydroperoxy-3,7-dimethylocta-2,7-dienal
-H), 1.41 d.d (2H, 5-H), 1.45 m (2H, 6-H), 1.82 m
1
(
5
8
Id). H NMR spectrum, δ, ppm: 1.71–1.76 m (8H,
-H, C H , C H ), 1.98 br.s (2H, 4-H), 3.32 m (2H,
-H), 4.93 br.s (1H, 6-H), 4.97 d (1H, 2-H, J = 8 Hz),
(
5
1H, 1-H), 1.99 m (1H, 4-H), 2.75 d (1H, 8-H, J =
Hz), 2.78 d (1H, 8-H, J = 5 Hz). GC–MS data: reten-
tion time 17.917–19.233 min; m/z (I , %): 152 (5)
9
10
3 3
rel
+
+
+
8.05 s (1H, OOH), 9.97 d (1H, CHO, J = 8 Hz).
[
(
[
(
M] , 137 (50) [M – CH ] , 123 (7) [M – CO] , 119
3
+
+
5) [M – C H ] , 109 (100) [M – C H O] , 108 (48)
M – C H O] , 94 (25) [C H ] ; 85 (80), 67 (80), 65
2-(1-Hydroperoxy-1-methylethyl)-5-methyl-
2
9
2
3
+
+
2
4
7
10
cyclohex-2-en-1-one (IIb). Colorless oil, C H O
10 16
3
+
–1
15) [C H ] .
(M 184.238). IR spectrum, ν, cm : 3442, 2956, 2871,
5
5
1
1
662, 1110. H NMR spectrum, δ, ppm: 1.07 d (3H,
Camphor (IIIb). Colorless crystals, mp 180°C,
–
1
7
8
9
C H O (M 152.238). IR spectrum, ν, cm : 3456,
C H , J = 7 Hz), 1.38 s (3H, C H ), 1.46 s (3H, C H ),
3 3 3
1
0
16
1
2
0
949, 1704, 1445, 1047. H NMR spectrum, δ, ppm:
.84 s (3H, C H ), 0.91 s (3H, C H ), 0.96 s (3H,
C H ), 1.38 m (2H, 5-H), 1.69 d.d.d (2H, 6-H, J = 4, 9,
1.68 d.d.d.d (1H, 4-H, J = 3, 10, 10, 18 Hz), 2.03 d.d
(1H, 6-H, J = 3, 10 Hz), 2.15 m (2H, 5-H, 6-H),
2.36 d.d.d.d (1H, 4-H, J = 3.6, 5, 5, 18 Hz), 3.49 br.s
9
10
3
3
8
3
1
2
3 Hz), 1.84 d (1H, 3-H, J = 18 Hz), 1.94 m (1H, 4-H),
(1H, OH), 5.51 d.d (1H, 3-H, J = 3, 3.6 Hz), 8.8 s
13
13
.35 d.t (1H, 3-H, J = 4, 18 Hz). C NMR spectrum,
C NMR spectrum, δ , ppm: 21.24
(
1H, OOH).
C
8
9
10
7
8
9
5
δ , ppm: 9.3 (C H ), 19.1 (C H ), 19.7 (C H ), 27.0
C
3
3
3
(C H ), 25.48 (C H ), 25.61 (C H ), 28.28 (C ), 33.63
(
1
3 3 3
5
6
4
7
3
4
6
10
3
2
(
(
C ), 29.9 (C ), 43.0 (C ), 43.6 (C ), 48.0 (C ), 57.7
C ), 219.7 (CO). GC–MS data: retention time 15.690
C ), 38.60 (C ), 82.30 (C ), 119.56 (C ), 149.80 (C ),
99.53 (CO). GC–MS data: retention time 16.626 min:
1
+
+
min; m/z (I , %): 152 (95) [M] , 137 (30) [M – CH ] ,
1
+
+
rel
3
m/z (I , %): 184 (2) [M] , 166 (6) [M – H O] , 153
rel
2
+
+
23 (5) [M – C H ] , 109 (70) [M – C H ], 95 (20)
+
+
2
5
3
7
(
[
(
100) [M – CH O] , 137 (15) [M – CH O ] , 135 (15)
3 3 2
+
[
M – C H ], 81 (100) [M – C H ], 67 (70) [M –
+
+
+
4
9
5
11
M – CH O ] , 94 (5) [C H O] , 66 (5) [C H ] , 43
5
2
6
6
5
6
+
C H ], 41 (30) [C H ] .
+
6
14
3
5
35) [C H ] .
3
7
Photosensitized oxygenation of natural terpenes
2
-Hydroperoxy-5-methyl-2-(1-methylethenyl)-
cyclohexan-1-one (IIc). Colorless oil, C H O
3
I and II (general procedure). A solution of 0.01 mol
of compound I or II in chloroform or ethanol contain-
ing the corresponding singlet oxygen sensitizer was
irradiated at –5°C using a sodium lamp, a continuous
stream of dry oxygen being passed through the solu-
tion at a low rate to avoid evaporation of the mixture.
The solvent was removed under reduced pressure
1
0
16
–
1
(
1
(
M 184.238). IR spectrum, ν, cm : 3418, 2960, 2871,
704, 1451, 1160. H NMR spectrum, δ, ppm: 1.00 d
3H, C H , J = 6 Hz), 1.4 m (2H, 4-H), 1.80 s (3H,
C H ), 2.00 m (1H, 5-H), 2.2 m (2H, 3-H), 2.5 m (2H,
1
7
3
8
3
6
2
-H), 5.0 d (1H, 9-H, J = 20 Hz), 5.15 d (1H, 9-H, J =
1
3
0 Hz), 9.85 s (1H, OOH). C NMR spectrum, δ ,
(
15 mm) at 20°C, and the residue was subjected to
C
8
7
3
5
ppm: 18.0 (C H ), 19.0 (C H ), 21.5 (C ), 28.5 (C ),
3
column chromatography on silica gel using petroleum
ether (bp 60–80°C)–diethyl ether (9:2) as eluent. In
the reaction with citral (I) we isolated compounds Ic
and Id, and in the reaction with pulegone (II), com-
pounds IIa/IIa′, IIb, and IIc. The reaction conditions
3
3
4
6
2
9
1.3 (C ), 47.7 (C ), 116.8 (C ), 119.5 (C ), 141.6
1
0
(
C ), 208.0 (CO). GC–MS data: retention time
+
19.053 min; m/z (I
[M – H
CH
81 (99) [C
rel, %): 184 (2) [M] , 166 (50)
+
+
O] , 152 (100) [M – CH
O] , 137 (35) [M –
2
+
2
+
+
(
solvent, sensitizer, reaction time) and yields of the
3
O
2
] , 135 (15) [M – CH
5
O
2
] , 95 (60) [C
6
H
7
O] ,
+
+
+
photoproducts are given in table.
5
H
5
O] , 66 (10%) [C
5
H ] , 43 (30) [C H ] .
6 3 7
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008

8
22
ELGENDY, KHAYYAT
Study on photoinduced DNA damage in the
11. Richter, S., Gatto, B., Fabris, D., Takao, K.-i.,
Kobayashi, S., and Palumbo, S.M., Nucleic Acids Res.,
003, vol. 31, no. 17, p. 5149.
presence of hydroperoxides Ic and 2b. A solution of
DNA in saline, 1 ml, was added to a solution of 1 mg
of hydroperoxide Ic or 2b in 5 ml of ethanol. The
mixture was irradiated for 8 h at 0°C using a sodium
lamp, and samples were withdrawn at definite time
intervals to determine the damaging effect by the gel
electrophoresis technique [24]. The photographs of the
gel were taken under UV light (λ = 365 nm). Com-
pound Ic induced a moderate degree of DNA damage
after irradiation for 8 h, and compound IIb showed
a moderate degree of DNA damage after irradiation for
2
1
1
1
1
2. Yarovaya, O.I., Korchagina, D.V., Salomatina, O.V.,
Polovinka, M.P., and Barkhash, V.A., Mendeleev Com-
mun., 2003, p. 27.
3. Yarovaya, O.I., Korchagina, D.V., Gatilov, Yu.V., and
Barkhash, V.A., Russ. J. Org. Chem., 2002, vol. 38,
no. 6, p. 810.
4. Asthana, A., Larson, R. A., Marley, K.A., and Tuve-
son. R.W., Photochem. Photobiol., 1992, vol. 56, no. 2,
p. 211.
5. Tisserand, R.B. and Balacs, T., Essential oil Safety:
A Guide for Health Care Professionals, Edinburgh:
Churchill Livingstone, 1995, p. 147.
5
h and high degree of DNA damage after irradiation
for 8 h.
1
1
1
6. Schaneberg, B.T. and Khan, I.A., J. Agric. Food Chem.,
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008