Synthesis of (-)-3-carene-2,5-dione via allylic oxidation of (+)-3-carene

Article abstract of DOI:10.1002/jccs.201100694

Activated carbon-supported CuCl₂ (CuCl₂/AC) is a heterogeneous catalyst for the liquid-phase selective allylic oxidation of (+)-3-carene with tert-butyl hydroperoxide (TBHP) and O₂ to produce (-)-3-carene-2,5-dione. The possible reaction mechanism and the effects of different factors on the allylic oxidation were investigated. The optimal conditions are as follows: reaction temperature, 45 °C; molar ratio of CuCl₂ to (+)-3-carene, 1%; volume ratio of (+)-3-carene to TBHP, 1:3; and reaction time, 12 h. Under the optimal conditions, the conversion of (+)-3-carene reached 100%, whereas the selectivity for (-)-3-carene-2,5-dione reached 78%. The CuCl₂/AC catalyst was characterized via X-ray diffraction, and the chemical structure of the target compound was identified via infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectrometry, and optical analysis.

Full text of DOI:10.1002/jccs.201100694

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Article
Synthesis of (-)-3-Carene-2,5-dione via Allylic Oxidation of (+)-3-Carene
Xiaoling Sun,* Xiaoyan Zhao, Ying Jiang and Bochun Xu
School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China
(Received: Nov. 28, 2011; Accepted: Jun. 22, 2012; Published Online: ??; DOI: 10.1002/jccs.201100694)
Activated carbon-supported CuCl2 (CuCl2/AC) is a heterogeneous catalyst for the liquid-phase selective
allylic oxidation of (+)-3-carene with tert-butyl hydroperoxide (TBHP) and O2 to produce (-)-3-carene-
2,5-dione. The possible reaction mechanism and the effects of different factors on the allylic oxidation
were investigated. The optimal conditions are as follows: reaction temperature, 45 °C; molar ratio of
CuCl2 to (+)-3-carene, 1%; volume ratio of (+)-3-carene to TBHP, 1:3; and reaction time, 12 h. Under the
optimal conditions, the conversion of (+)-3-carene reached 100%, whereas the selectivity for (-)-3-
carene-2,5-dione reached 78%. The CuCl2/AC catalyst was characterized via X-ray diffraction, and the
chemical structure of the target compound was identified via infrared spectroscopy, proton nuclear mag-
netic resonance spectroscopy, mass spectrometry, and optical analysis.
Keywords: Activated carbon-supported CuCl2; (-)-3-Carene-2,5-dione; (+)-3-Carene; Allylic oxi-
dation; Mechanism.
INTRODUCTION
Allylic oxidation is an important and useful reaction
carene with either oxygen or TBHP as the oxidant, obtain-
ing 51% selectivity after 48 h. The major drawback of these
systems is the overly long reaction time. Oliveira7 reported
that the PdCl-catalyzed allylic oxidation of (+)-3-carene
with H2O2 in CH3CN solutions has a conversion of 47% af-
ter 10 h. Although the reaction time is not very long, the
conversion is quite low, and the oxidant, H2O2, is highly ex-
plosive. In addition, because of the serious environmental
problems associated with chromium- and selenium-con-
taining effluents, attention has focused on environmentally
safe catalysts for the allylic oxidation of (+)-3-carene. Car-
bon-supported Cu-based catalysts can be used in vapor
phase reactions,8–12 with oxygen as one of the oxygenants.
Thus, a novel catalyst composed of activated carbon-sup-
ported CuCl2 (denoted as CuCl2/AC) was prepared and
characterized via powder X-ray diffraction (XRD). The al-
lylic oxidation of (+)-3-carene to (-)-3-carene-2,5-dione by
an O2-TBHP system using CuCl2/AC as an active, selec-
tive, and recyclable catalyst is also reported. Not only was
the reaction time reduced, but the selectivity of the (-)-3-
carene-2,5-dione product was also enhanced.
in many areas of organic synthesis.1 (-)-3-Carene-2,5-di-
one, one of the products of allylic oxidation of (+)-3-ca-
rene[(1S,6R)-3,7,7-trimethylbicyclo[4.1.0]hept-3-ene] of-
ten serves as the starting material for the synthesis of fra-
grances and flavors, as well as of synthetic intermediates
and chiral building blocks.2 (+)-3-Carene is an interesting
substrate for oxidation reactions because it can undergo
several different modes of attack by the oxidant, such as,
e.g. epoxidation or oxidative cleavage of the double bond,
or the oxidation of allylic C-H bonds. Different catalysts
and oxidants can be used in the allylic oxidation of (+)-3-
carene to synthesize the desired product selectively. For ex-
ample, Robles-Dutenhefner3 used sol-gel Co/SiO2 as a cat-
alyst for the allylic oxidation of (+)-3-carene with oxygen
under solvent-free conditions, achieving only 10% selec-
tivity. Catir4 reported the allylic oxidation of (+)-3-carene
to (-)-3-carene-2,5-dione with a system of bis(trifluoroace-
toxyiodo)benzene and tert-butyl hydroperoxide (TBHP),
achieving high conversion (90%) but low selectivity (35%).
In these two studies, (-)-3-carene-2,5-dione was obtained
with very low selectivity. Shing5 was able to obtain high se-
lectivity (60%) in the mild manganese(III) acetate-cata-
lyzed allylic oxidation of (+)-3-carene to (-)-3-carene-2,5-
dione after 48 h reaction time. Lempers6 reported the use of
chromium-substituted aluminophosphate (CrAPO-5) as an
active, selective catalyst for the allylic oxidation of (+)-3-
EXPERIMENT
Instruments and raw materials
Most of the chemicals were purchased from China
Medicine (Group) Shanghai Chemical Reagent Corp., ex-
cept for (+)-3-Carene, CuCl2, and activated carbon, which
were purchased from Sigma-Aldrich. The Panalytical PW
* Corresponding author. E-mail: xiaolingsun1@msn.com
J. Chin. Chem. Soc. 2012, 59, 000-000
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Sun et al.
3040/60 X’Pert PRO diffractometer was used to character-
ize the catalyst. The GC-9790 II gas chromatograph was
used to monitor the oxidation reaction and analyze the reac-
tion product qualitatively and quantitatively. The Bruker
AVANCE III 500 MHz spectrometer, Agilent 5973N mass
spectrometer (MS), Magana-IR 500 Fourier transform in-
frared (FT-IR) spectrometer, and Rudolph Autopol III
polarimeter were all used to characterize the oxidation
product.
with the XRD spectra of fresh activated carbon. A number
of peaks for CuCl2/AC were detected at 2q = 16.2°, 21.9°,
28.88°, and 33.9°, thereby confirming its successful prepa-
ration.
Synthesis of (-)-3-carene-2,5-dione
The allylic oxidation of (+)-3-carene was conducted
in a 25 mL round-bottomed flask connected to a condenser
and a magnetic stirrer. (+)-3-Carene (1.7 g, 0.0125 mol),
TBHP (6 mL), acetonitrile (MeCN, 10 mL), and CuCl2/AC
(0.067 g, 12.5 mmol) were added into the flask, and the re-
action mixture was heated at 45 °C under an oxygen flow.
The reactions were analyzed using a gas chromatograph
(GC) equipped with a flame ionization detector and fitted
with an SE-54 capillary column (30 m × 0.53 mm). The GC
conditions were as follows: initial temperature, 80 °C (1
min); temperature rate, 5 °C/min; final temperature, 200
°C; injector temperature, 80 °C; and detector temperature,
200 °C. The amount of each compound in the reaction mix-
ture was estimated from the corresponding chromato-
graphic peak areas using chlorobenzene as the internal
standard, and by comparing with the corresponding cali-
bration curves. These calibration curves were constructed
using authentic samples or isolated compounds from the re-
action solution. The retention times were compared with
those of commercially available or previously synthesized
products. The experimental results showed that the main
oxidation products are (-)-3-carene-2,5-dione and (+)-3-
carene-5-one by a 10:1 ratio or better.
Catalyst preparation
The activated carbon support and CuCl2 used for cat-
alyst preparation were commercial products of chemically
pure grade. The CuCl2/AC catalysts were prepared via the
conventional impregnation method. Activated carbon and
CuCl2 were dried in vacuum to remove water. A copper
chloride solution was prepared by dissolving CuCl2 (1 g,
5.8 mmol) in ethanol (10 g). The activated carbon particles
(3 g, 0.25 mol) were then impregnated with the copper
chloride solution. The resulting solution was stirred for
24 h under a nitrogen gas flow at room temperature, fol-
lowed by drying under nitrogen at 150 °C for 2 h. The dried
samples were then cooled to room temperature. Calcination
was performed by heating the powdered catalyst to 300 °C
at a rate of 1 °C/min in a stream of nitrogen, and the temper-
ature was held at 300 °C for 10 h. Morphological analysis
of the catalyst was conducted via XRD.
Catalyst characterization
The XRD patterns were recorded on a Panalytical PW
3040/60 X’Pert PRO diffractometer with Cu Ka radiation.
The diffraction patterns at 40 kV and 40 mA were recorded
within the 5° to 80° Bragg angle (2q) range at a rate of 5°/
min.
Pure (-)-3-carene-2,5-dione was obtained through sil-
ica column chromatography [eluting with a mixture of
ethyl acetate: petroleum ether (10:90)] as a pale yellow
needle crystal. [a] D23 = -9.428 (c 0.308, EtOH); 1H NMR
(CDCl3, 500 MHz) d: 1.33 and 1.33 (2s, 2×3 H, H-8, 9),
1.98 (s, 3H, H-10), 2.32–2.35 (m, 2H, H-1, 6), and 6.51 (q,
1H, H-4); IR (KBr) u: 3434, 3038, 2981, 2955, 2926, 1652,
and 1622 cm-1; MS (70 eV) m/z (relative intensity %): 164
(M+×, 57), 128 (100), 121 (55), 91 (50), 93 (69), 77 (41), 67
(44), and 53 (44). The data are in accordance with experi-
mental results reported in literature.13
Two activated carbon peaks were detected at 2q =
26.6° and 54.7° (Fig. 1). This peak pattern is in accordance
As a byproduct of oxidation of the (+)-3-carene, (+)-
3-carene-5-one was obtained through silica column chro-
matography as an orange oily material. [a] 2D3 = +153.51° (c
0.101 g/100 mL, AcOEt); 1H NMR (CDCl3, 500 MHz) d:
1.03 (s, 3H), 1.19 (s, 3H), 1.45 (t, 1H), 1.57 (d, 1H), 1.87 (s,
3H), 2.32 (d, 1H), 2.64 (d, 1H), and 5.83 (s, 1H). IR (KBr)
n (cm-1): 2959, 1658, 1440, 1379 cm-1. MS (EI) m/z (rela-
tive intensity %): 150 (M+×, 100), 135 (9.21), 121 (13.33),
Fig. 1. X-ray diffraction (XRD) patterns of fresh acti-
vated carbon (AC), pure CuCl2, and activated
carbon-supported CuCl2 (CuCl2/AC).
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Preparing (-)-3-Carene-2,5-dione from (+)-3-Carene
107 (11.34), 93 (100), 91 (53.38), 79 (37.74), 43 (35.69),
41 (34.69), 77 (33.98), 92 (31.17), 80 (29.04). The data are
in accordance with the results reported in literature.13
shows that the best result was obtained after 12 h reaction
time. When the reaction time is increased to 18 h, numerous
unidentified by-products are formed, and the product yield
decreases.
RESULTS AND DISCUSSION
Effect of the catalyst concentration
Effect of the reaction temperature
The previously determined optimized conditions
were applied to the experimental reactions using different
amounts of the catalyst to determine the optimal catalyst
amount. Fig. 4 shows that the best result was obtained at a
1% to 3% mole ratio of CuCl2/AC to (+)-3-carene. When
the catalyst amount is greater than 3%, the (-)-3-carene-
2,5-dione yield slightly changes, and excess amounts of the
catalyst leads to the decomposition of the product. Fig. 4
also shows that a catalyst amount between 1% and 3% has
negligible effect on the product yield. Therefore, 1% cata-
lyst was determined as the optimal amount.
The reaction is a gas-liquid-solid three-phase reac-
tion; thus, the temperature is the crucial factor that affects
the reaction. Therefore, the effect of the reaction tempera-
ture on the yield was investigated. Fig. 2 shows that the best
results were obtained at 45 °C. When the temperature in-
creases, the yield of the target product drops, and more by-
products are formed. When the temperature is increased,
the oxygen content in the solution is reduced, and the reac-
tion becomes inhibited. Therefore, 45 °C was determined
as the optimal reaction temperature.
Effect of the reaction time
Effect of the volume ratio of TBHP to (+)-3-carene
The amount of TBHP has significantly affects the re-
action rate. The effect of the volume ratio of TBHP to (+)-
3-carene on the reaction was determined. Fig. 5 shows that
3:1 is the best volume ratio of TBHP to (+)-3-carene. Side
reactions are likely to happen when an excess amount of
TBHP is present, resulting in reduced selectivity for (-)-3-
carene-2,5-dione. Therefore, 3:1 was determined as the op-
timal volume ratio of TBHP to (+)-3-carene.
The reaction processes were monitored via GC. Fig. 3
Effect of oxygen
Fig. 5 shows that some of the raw materials are oxi-
dized even when no TBHP is added to the reaction. This ob-
servation indicates the presence of another oxidant in the
reaction. This oxidant is oxygen. Therefore, the effect of
oxygen was determined through a pair of controlled experi-
ments, with one reaction conducted in the presence of oxy-
gen, and the other with no oxygen present. The reaction
Fig. 2. Effect of the reaction temperature on the prod-
uct yield (%). Conditions: 1.7 g (+)-3-Carene;
0.067 g CuCl2/AC; 6.0 mL tert-butyl hydroper-
oxide (TBHP); 10.0 mL acetonitrile (MeCN);
reaction time: 8 h; oxygen.
Fig. 3. Effect of the reaction time on product yield (%).
Conditions: 1.7 g (+)-3-carene; 0.067 CuCl2/
AC; 6.0 mL TBHP; 10.0 mL MeCN; tempera-
ture: 45 °C; oxygen.
Fig. 4. Effect of the catalyst amount on the product
yield (%). Conditions: 1.7 g (+)-3-carene; 6.0
mL TBHP; 10.0 mL MeCN; temperature: 45
°C; reaction time: 12 h; oxygen.
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Sun et al.
processes were monitored via GC within 14 h. The results
(Fig. 6) show that oxygen is an important factor in the
reaction.
Mechanism of allylic oxidation of (+)-3-
carene
Scheme I
Reaction mechanism
The proposed reaction mechanism is as follows
(Scheme I). According to the type of oxidant (t-BuOOH
and CuCl2) and the proportion of alcohol and ketone
(higher selectivity for ketone), we considered that that the
reaction is one of the Gif oxidation system, namely
GoChAggII. The mechanism is similar to that proposed for
other Gif-typ reactions.14-15
Oxidation of a-pinene and cyclohexene
Under the same optimal conditions, verbenone was
also synthesized via the allylic oxidation of a-pinene, with
a yield of 28%; cyclohexenone was also synthesized via the
allylic oxidation of cyclohexene, with a yield of 13.8%
Fig. 5. Effect of the volume ratio of TBHP to (+)-3-
carene on the product yield (%). Conditions:
1.7 g (+)-3-carene; 0.067 g CuCl2/AC; 10.0 mL
MeCN; temperature: 45 °C; reaction time: 12 h;
oxygen.
(Scheme II). Moreover, when the temperature is increased
to 70 °C, the yields of verbenone and cyclohexenone in-
crease to 76.7% and 23.1%, respectively.
Fig. 6. Effect of oxygen on the product yield (%). The
red and black lines indicate the yield in the
presence and absence of oxygen, respectively.
Conditions: 1.7 g (+)-3-carene; 0.067 g CuCl2/
AC; 10.0 mL MeCN; temperature: 45 °C.
Verbenone was characterized via 1H NMR. (500.15
MHz, CDCl3) d: 1.02 (s, 3H); 1.46 (s, 3H); 2.00 (s, 3H);
4
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Preparing (-)-3-Carene-2,5-dione from (+)-3-Carene
Allylic oxidation of a-pinene and cyclo-
Scheme II
friendly, and highly economical method of preparing (-)-
3-carene-2,5-dione has been developed in this study.
hexene
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(-)-3-Carene-2,5-dione can be synthesized via the al-
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O2 in a solution of MeCN. Single-factor experiments were
designed to optimize the synthesis conditions and obtain
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carene, 1%; volume ratio of (+)-3-carene to TBHP, 1:3; and
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