Ozonolysis of 3-caren-5-one

Article abstract of DOI:10.1023/A:1012383030120

Cleavage by ozonolysis of a cyclic unsaturated ketone, 3-caren-5-one, was investigated under different conditions. The main reaction product is ketocaronic acid. A scheme of ketocaronic acid formation was suggested basing on kinetics of ozone reaction with 3-caren-5-one and thermal decomposition of peroxides.

Full text of DOI:10.1023/A:1012383030120

Russian Journal of Organic Chemistry, Vol. 37, No. 2, 2001, pp. 238 242. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 2, 2001,
pp. 251 255.
Original Russian Text Copyright
2001 by Galin, Kukovinets, Zainullin, Shershovets, Kashina, Akhmetov, Kunakova, Tolstikov.
Ozonolysis of 3-Caren-5-one
F. Z. Galin, O. S. Kukovinets, R. A. Zainullin, V. V. Shershovets,
Yu. A. Kashina, A. M. Akhmetov, R. V. Kunakova, and G. A. Tolstikov
Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, Ufa, Bashkortostan, 450054 Russia
Received April 24, 2000
Abstract Cleavage by ozonolysis of a cyclic unsaturated ketone, 3-caren-5-one, was investigated under
different conditions. The main reaction product is ketocaronic acid. A scheme of ketocaronic acid formation
was suggested basing on kinetics of ozone reaction with 3-caren-5-one and thermal decomposition of
peroxides.
The ozonolysis of cyclic olefins provides a pos-
sibility to prepare under mild conditions , -bi-
functional oxygen-containing compounds fit for
further syntheses. For instance, starting with the
ozonolysis products of chiral cyclic terpenes, (+)- -
pinene and (+)-3-carene, were carried out the syn-
theses of optically active pheromones, juvenoids, and
pyrethroids [1, 2]. The ozonolysis of cyclic un-
saturated ketones considerably differs from that of
cyclenes, and it is relatively poorly investigated. The
study of ozone cleavage of 3-caren-5-one that is
produced by (+)-3-carene oxidation in the liquid
phase [3] would extend the number of these reactions
and provide a possibility to obtain new derivatives
possessing useful properties.
According the data on some cases of ozonolysis
carried out with , -unsaturated cyclic ketones [4]
the reaction took an abnormal course with CO2
ejection. We established that from the reaction of
excess ozone with carenone (I) in a fair yield was
obtained ( )-(1R,3S)-2,2-dimethyl-3-(2-oxopropyl)-
cyclopropanecarboxylic acid (II) [3].
Several attempts were made to rationalize this
reaction course. For instance, a possible mechanism
ene ozonolysis involving an ejection of carbon
oxides and a stabilization of an intermediate zwitter-
ion IV.
[5] was suggested by an example of polyphenylacetyl-
1
070-4280/01/3702-0238$25.00 2001 MAIK Nauka/Interperiodica

OZONOLYSIS OF 3-CAREN-5-ONE
239
Fig. 1. Kinetics of peroxides accumulation at ozonization
of carenone (I) in CH CN at 20 C (1) and 22 C (2),
3
1
carenone c0 0.24 mol l .
However the lack in the reaction products of com-
pound IX and the requirement of twofold excess of
ozone for obtaining acid II in high yield permitted us
to presume that the reaction took another route
involving the formation of a new double bond
consuming the second molar equivalent of ozone in
its cleavage.
Our assumption was corroborated by kinetic study
of ozone consumption and ozonides accumulation
(
Fig. 1). The ozone consumption after complete
disappearance of 3-caren-5-one (I) was due to deeper
oxidation of unsaturated ketone (I), and to obtain the
maximum yield of ketoacid II was required at least
a double ozone excess. The character of the curves of
ozone consumption and ozonides accumulation
evidences that the rates of ozone reaction with sub-
strate and the primary product of its oxidation are
different. The high rate of ozone consumption at the
beginning of the reaction is due to sufficiently
effective compensation by the inductive effect of the
methyl group of the displacement of the double bond
electron density to the carbonyl carbon atom. Beside
the electronic effects the reaction rate is affected by
steric factors due to the shielding of the keto group
in zwitterion VIII by the bulky gem-dimethylcyclo-
propane fragment of the molecule. Therefore the
stabilization of the zwitterion by formation of ozonide
Fig. 2. Kinetics of peroxides decomposition in CH CN at
3
2
0 C (1) and 22 C (2) at O olefin molar ratio 2.7 (1)
3
and 3.1 (2).
Razumovskii et al. assume that the key stage of
the process is the rearrangement of zwitterion IV
resulting in excited state of phenylglyoxalic acid
(
Va). The molecule may be stabilized either by dis-
sipation of the energy excess and formation of a
stable ketocarboxylic acid Vb or by ejection of carbon
oxides and formation benzoic acid (VI) or benz-
aldehyde (VII). At the same time the bipolar ion IV
and acid Vb in the course of the experiment do not
react with ozone, and this permits to exclude the
possibility of oxidative cleavage of acid Vb by ozone.
In keeping with this mechanism it should be expected
that in ozonolysis of carenone (I) alongside ketoacid
II form a comparable amount of diketoacid IX.
X becomes improbable. The rates of O absorption
3
and of peroxides formation notably decrease after
complete disappearance of the initial ketone I from
the reaction mixture: It is evidenced by a definite
bend on the curves of ozone consumption and per-
oxides accumulation (Fig. 1).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 2 2001

2
40
GALIN et al.
1
The study of thermal stability of ozonides obtained
In the H NMR spectrum at 3.25 and 3.38 ppm
appear signals from 12 protons of the dimethoxy
groups. In the 13C NMR spectrum of the compound
the signal at 53.97 ppm corresponds to the dimethoxy
group close to the keto group, and at 51.88 ppm to
that far from the keto group. The chemical shift of the
carbonyl carbon is 204.55 ppm. If the amount of the
ozone-oxygen mixture passed through the solution of
at different ratios O 3-caren-5-one showed that in
the reaction products were present at least two kinds
of peroxides (Fig. 2).
3
We believe that in bipolar intermediate VIII the
keto groups in -position with respect to the reaction
site favor its stabilization in the form of peroxyenol
XI. This is in agreement with the published data that
1
,2-dicarbonyl compounds are prone to enolization
ketone XIV is increased to 12 mol equiv of O per
3
[
6, 7]. The sole product of enolate XI ozonolysis is
1 mol of alkene the above workup procedure afforded
ketoacid II. The decrease in ozone absorption at the
second reaction rate may be ascribed to electron
deficiency of the double bond in the peroxide inter-
mediate XI.
methyl 5,5-dimethoxypentanoate (XV). In the
1
3
C NMR spectrum of compound XV appears a signal
at 3.52 ppm twice less intensive compared to the
signals of dimethoxy groups at 3.25 ppm and equal
in intensity to that of CH O of the ester group of
In order to corroborate the assumed reaction
mechanism and to establish the substituents effect we
studied the ozonolysis of 1-methylcyclohexene (XII)
and cyclohexenone (XIV).
3
compound XV. In the 13C NMR spectrum of the
compound the carboxy group carbon gives a peak at
173.35 ppm, and the characteristic signal of keto
group in 200 ppm region is lacking. The mass spec-
trum also is consistent with the assumed structure.
Obviously the conjugation of the double bond and
the carbonyl group is decisive for the route of
ozonolytic cleavage of cyclohexenes. At the same
time it should be noted that the presence of an
electron-acceptor group reduces the electron density
on the double bond and therewith considerably
decelerates the ozone attack thereto. In carenone (I)
the gem-dimethylcyclopropane fragment of the
molecule largely compensates the displacement of the
electron density of the double bond to the carbonyl
carbon and thus facilitates the ozone addition and
accelerates the reaction.
After absorption of one mol equiv of ozone with
-methylcyclohexene (XII) in methanol at 75 C
followed by reduction of the peroxide ozonolysis
product with hydrogen on Lindlar catalyst was
obtained ketoaldehyde XIII.
1
The crucial difference was observed in the reaction
products of ozone with cyclohexen-2-one (XIV).
After passing 3 mol equiv of ozone through the
methanol solution of ketone XIV at 40 C followed
by reduction of the peroxide reaction products with
dimethyl sulfide and boiling of the reaction mixture
in methanol with p-toluenesulfonic acids we separated
EXPERIMENTAL
IR spectra of compounds were registered on
UR-20 spectrophotometer from thin film. The
specific rotation was measured on Perkin-Elmer 141
1
,1,6,6-tetramethoxy-2-hexanone (XVI). Its structure
1
13
was proved by H and C NMR spectroscopy.
1
instrument in CHCl3 solutions. H NMR spectra
were recorded on spectrometer Tesla BS-576
(
100 MHz), 13C NMR spectra were run on spectro-
meter JEOL FX-90 Q (22.5 MHz), solvent CDCl3,
internal reference TMS. GLC was carried out on
chromatograph Chrom-5, column 1200 4 mm,
stationary phase 5% SE-30 on Chromaton N-AW-
DMCS, oven temperature 50 300 C, carrier gas
helium. Mass spectrum was measured on MKh-1320
instrument at ionizing electrons energy 70 eV.
Elemental analyses of compounds obtained were in
agreement with the calculated figures.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 2 2001

OZONOLYSIS OF 3-CAREN-5-ONE
241
(
)-(1R,3S)-2,2-Dimethyl-3-(2-oxopropyl)cyclo-
propanecarboxylic acid (II). Through a solution of
.45 g (3 mmol) of 3-caren-5-one (I) in 10 ml of
distilled off at 10 mm Hg, the residue was dissolved
in ether, the solution was washed with water, dried
0
with MgSO , and the ether was distilled off. We
4
anhydrous acetonitrile at 0 C was bubbled an ozone-
obtained 16.2 g (91%) of 2-oxoheptanal (XIII)
2
0
oxygen mixture (1.5 2 wt% of O ) at the flow rate
dimethylacetal, bp 55 60 C (1 mm Hg), n 1.4297.
3
D
.4 l h 1 till the end of ozone absorption. The ozone
1
5
IR spectrum ( , cm ): 840, 960, 1060, 1705.
H NMR spectrum ( , ppm, J, Hz): 1.58 m (6H,
1
concentration at the input and output of the reactor
was monitored by iodometric titration. On completion
of reaction the reaction mixture was flushed with
argon, then 0.31 g (2.48 mmol) of Na SO was
CH ), 1.98 s (3H, CH CO), 2.45 m (2H, CH CO),
2
3
2
3.10 s (6H, OCH ), 4.18 t (1H, OCHO, J 5.5 Hz).
3
+
2
3
Mass spectrum, m/z (I , %): 174 [M] (0.1), 173
rel
+
+
added, and the mixture was left standing at room
temperature till complete reduction of peroxides (till
negative test with the acidified aqueous solution of
KI). The reaction mixture was filtered, the solvent
was distilled off, and to the residue was added by
(
1
5.0), 156 [M H O] (40.0), 143 [M OCH ] (10.1),
2 3
+
10 [M 2CH OH] (6.2), 75 (100).
3
Methyl 5,5-dimethoxypentanoate (XV). Through
a solution of 1 g (10.42 mmol) of 2-cyclohexenone
XIV) in 15 ml of anhydrous methanol at 40 C was
bubbled an ozone-oxygen mixture (5 wt% of O ) until
(
portions 15 ml of concentrated NaHCO solution till
3
CO evolution ceased. Then the reaction mixture was
3
2
1
2 mmol of O was consumed per 1 mmol of cyclo-
washed with ethyl ether (3 50 ml), the water solu-
tion was acidified with50% H SO till pH 2 3, and
3
hexenone XIV. The reaction mixture was flushed
2
4
with argon, 1,14 ml (15.53 mmol) of (CH ) S was
the organic layer was separated. Into the remaining
water layer was added NaCl till saturation, acid II
was extracted with ethyl ether (3 50 ml). The
combined organic solutions were washed with water
3 2
added, the mixture was stirred for 1 h and left stand-
ing at room temperature for 12 h. The solvent was
distilled off, the residue was dissolved in 50 ml of
anhydrous methanol and boiled for 3 h in the
presence of 0.012 g (0.07 mmol) of p-toluenesulfonic
and dried on MgSO . On distilling off the solvent we
4
obtained 0.74 g of oily substance that was subjected
to column chromatography on SiO (eluent hexane
acid. Then a solution of CH ONa in methanol was
2
3
2
4
ether, 1: 1). Yield of ketoacid 0.44 g (60%); n
added till stable alkaline pH, methanol was distilled
off at 10 mm Hg. The residue was dissolved in ether,
the solution was washed with water, and dried on
D
2
2
1
(
1
.4750, [ ]
32 (c 1.0, CHCl ). IR spectrum
D
3
1
, cm ): 1130, 1180, 1240, 1370 1380, 1450,
700 1730, 2400 3600. H NMR spectrum ( , ppm,
1
MgSO . On removing the solvent we obtained 1.21 g
4
2
J, Hz): 1.17 s (3H, -CH C ), 1.24 s (3H,
of oily reaction product that was subjected to vacuum
distillation to afford 0.41 g (22%) of ester XV, bp
3
2
1
3
-
CH C ), 1.45 1.65 m (2H, C H, C H), 2.18 s
3
38 C (3 mm Hg), n1 1.4491. IR spectrum ( , cm ):
7
1
(
3H, CH CO), 2.80 3.00 q.d (2H, CH , J 33.01,
3 2 ,
D
1
J
18.9, J2,10 6.73 Hz), 11.08 s (1H, CO H).
1150, 1220, 1370 1380, 1460, 1715 1750. H NMR
spectrum ( , ppm): 1.52 m (2H, C H2), 1.83 m (2H,
2
3
,1
2
1
2
4
C NMR spectrum ( , ppm): 14.24 ( -C ), 26.45
C
2
3
2
1
3
2
(
(
C ), 27.96 (C ), 28.45 ( -C ), 28.52 (C ), 29.92
C ), 37.94 (C ), 178.33 (C ), 208.60 [C(O)O].
C H ), 2.22 m (2H, C H ), 3.16 s (6H, OCH ), 3.52
2 2 3
3
1
2
13
m [3H, C(O)OCH ], 4.22 t (1H, OCHO). C NMR
3
spectrum ( , ppm): 19.72 (C ), 31.51 (C ), 33.58
C ), 51.31 (C O), 52.31 ( C_ O C ), 103.87 (C ),
73.35 (C ). Mass spectrum, m/z (I , %): 145
M OCH3] (5.8), 128 [M OCH OH] (2.9), 113
3.6), 101 [M 75] (3.9), 75 [(CH O) CH] (100),
3
4
C
2
-Oxoheptanal (XIII). Through a solution of 10 g
2
5
5
(
(104 mmol) of 1-methyl-1-cyclohexene (XII) in
1
1
[
(
rel
150 ml of methanol at 70 C was bubbled an ozone-
+
+
3
oxygen mixture (5 wt% of O ) at a flow rate 5.4 l h
+
3
+
3
2
till the solution got blue. The reaction mixture was
flushed with argon, 0.5 g of Lindlar catalyst was
added, and the reaction mixture was stirred under
hydrogen atmosphere till negative test for peroxides
with acidified water solution of KI. The catalyst was
filtered off. The purification and identification of
ketoaldehyde XIII was carried out by converting it
into dimethylacetal by treating the filtrate with 8.7 g
71 (36.9), 58 (56.9).
1, 1, 6, 6-Tetramethoxy-2-hexanone (XVI).
Through a solution of 1 g (10.42 mmol) of 2-cyclo-
hexenone (XIV) in 15 ml of anhydrous methanol at
40 C was bubbled an ozone-oxygen mixture (5 wt%
of O ) until 3 mmol of O was consumed per 1 mmol
3
3
of cyclohexenone XIV. The reaction mixture was
flushed with argon, 1,14 ml (15.53 mmol) of (CH3)2S
was added, the mixture was stirred for 1 h and left
standing at room temperature for 12 h. The solvent
(
162 mmol) of NH Cl and keeping it standing for
4
2
4 h. Then a solution of CH ONa in methanol was
3
added till stable alkaline reaction. Methanol was
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 2 2001

2
42
GALIN et al.
was distilled off, the residue was dissolved in 50 ml
of anhydrous methanol and boiled in the presence of
REFERENCES
0
.012 g (0.07 mmol) of p-toluenesulfonic acid till the
disappearance of the initial cyclohexenone XIV
TLC monitoring; Silufol, ethyl-acetate hexane,
: 1). Then a solution of CH ONa in methanol was
1. Odinokov, V.N.,, Bashk. Khim. Zh., 1994, vol. 1,
no. 3, pp. 29 33.
. Makaev, F.Z., Galin, F.Z., and Tolstikov, G.A., Izv.
Akad. Nauk, Ser. Khim., 1996, no. 3, pp. 517 518.
2
3
(
1
3
. Galin, F.Z., Kukovinets, O.S., Shereshovets, V.V.,
added till stable alkaline pH, methanol was distilled
off at 10 mm Hg. The residue was dissolved in ether,
the solution was washed with water, and dried on
,
Safiullin, R.L., Kukovinets, A.G., Kabal nova, N.N.,
,
Kasradze, V.G., Zaripov, R.N., Kargapol tseva, T.A.,
Kashina, Yu.A., and Tolstikov, G.A., Zh. Org. Khim.,
996, vol. 32, no. 10, pp. 1482 1485.
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New York: Academic Press, 1978, pp. 234 236.
5. Razumovskii, S.D. and Zaikov, G.E., Ozon i ego
reaktsii s organicheskimi soedineniyami (Ozon and Its
Reaction with Organic Compounds), Moscow: Nauka,
974, pp. 150 152.
6. Zavarzin, I.V., Klimova, T.A., Krayushkin, M.V.,
MgSO . On removing the solvent we obtained 1.32 g
4
1
of reaction product that was subjected to vacuum
distillation to afford 0.67 g (30%) of tetramethoxy-2-
4
1
7
hexanone (XVI), bp 80 95 C (2 mm Hg),
n
D
1
1
1
.4410. IR spectrum ( , cm ): 1150, 1220, 1330,
380, 1460, 1715, 1730. H NMR spectrum ( ,
1
ppm): 1.56 m (6H, CH ), 3.25 m [6H, CH OC(O)],
2
3
1
6
3
.38 s (6H, CH O), 4.32 m (1H, OC HO), 4.43 s
1H, OC HO). C NMR spectrum ( , ppm): 17.3
C ), 31.13 (C ), 36.14 (C ), 51.88 ( C_ O C ), 53.97
C_ O C ), 103.45 (C ), 103.58 (C ), 204.55 (C ).
3
1
13
,
(
(
(
C
Sevast yanova, V.V., and Novikov, S.S., Abstracts of
4
5
3
6
Papers, IV Vsesoyuznaya konferentsiya, posvyashchen-
naya 85-letiyu so dnya rozhdeniya akademika AN Latv.
SSR G. Vanaga (4th All-Union Conf. Devoted to 85
Years Jubiley of Acad. G. Vanag), Riga, 1976, p. 52.
7. Fliszar, S. and Granger, M., J. Am. Chem, Soc.,
1969, vol. 91, no. 12, pp. 3330 3337.
1
6
1
2
Mass spectrum, m/z (I , %): 221 (2.5), 203
rel
[
1
1
M OH]+ (65.0), 214 (3.7), 189 [M CH O] (6.7),
+
3
+
73 (2.7), 157 (1.3), 145 [M CH(OCH ) ] (0.9),
44 (5.8), 130 (6.2), 75 [CH(OCH ) ] (100).
3
2
3
2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 2 2001