Solvent-free isomerization of 3-carene to 2-carene using Na/o-chlorotoluene catalyst in trans-isolimonene production

Article abstract of DOI:10.13005/ojc/330652

Trans-isolimonene is one of the important compound in drugs development. This compound can be made by isomerization of inexpensive 3-carene via 2-carene using Na/o-chlorotoluene catalyst in xylene. The existence of xylene as a solvent requires a further separation process that can reduce the efficiency when applied in the bulk industry. The isomerization of 3-carene to 2-carene has been studied in solvent free reaction compared by isomerization without xylene solvent. The result showed that the isomerization can also occur in solvent-free condition. Solventfree isomerization gave 27.72% of conversion and 83.27% of selectivity while isomerization with solvent gave 23.59% of conversion and 86.87% of selectivity.

Full text of DOI:10.13005/ojc/330652

ISSN: 0970-020 X
CODEN: OJCHEG
017, Vol. 33, No.(6):
Pg. 3107-3111
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
2
www.orientjchem.org
Solvent-Free Isomerization of 3-carene to 2-carene using
Na/o-chlorotoluene Catalyst in Trans-isolimonene Production
1,3
1
1
TATANG SHABUR JULIANTO* , JUMINA , HARDJONO SASTROHAMID JOJO ,
and MUSTOFA2
1
Doctoral Program, Department of Chemistry, Faculty of Mathematics and Natural Sciences,
Gadjah Mada University, Jalan Sekip Utara, Yogyakarta, Indonesia.
2
Pharmacology and Therapy Unit, Department of Medicine, Gadjah Mada University,
Jalan Sekip Utara, Yogyakarta, Indonesia.
Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas
3
Islam Indonesia, Jalan Kaliurang Km.14,5 Yogyakarta, Indonesia.
*
Corresponding author E-mail: tatang_shabur@uii.ac.id
http://dx.doi.org/10.13005/ojc/330652
(Received: July 20, 2017; Accepted: August 10, 2017)
ABSTRACT
Trans-isolimonene is one of the important compound in drugs development. This compound
can be made by isomerization of inexpensive 3-carene via 2-carene using Na/o-chlorotoluene
catalyst in xylene. The existence of xylene as a solvent requires a further separation process that
can reduce the efficiency when applied in the bulk industry. The isomerization of 3-carene to
2
-carene has been studied in solvent free reaction compared by isomerization without xylene
solvent. The result showed that the isomerization can also occur in solvent-free condition. Solvent-
free isomerization gave 27.72% of conversion and 83.27% of selectivity while isomerization with
solvent gave 23.59% of conversion and 86.87% of selectivity.
Keywords: 3-carene, 2-carene, Na/o-chlorotoluene, xylene, trans-isolimonene, isomerization.
2
INTRODUCTION
synthesis of antimalarial drug artemisinin and
3
synthesis of menthol . These compounds is rarely
Trans-isolimonene is one of monoterpenoid
found naturally in plants. Several studies have
reported that isolimonene found in essential oils of
Citrus medica and Citrus reticulate. The peel oil of
compounds that a rare and little-studied substance.
1
It was first synthesized by Tshugaev in 1903 . Now
4,5
trans-isolimonene may become a fully accessible
monoterpenoid use as one of starting material for
some drug compounds development such as in
Citrus medica containi solimonene about 39.37%
6
and 5.87% in Citrus reticulate essential oil . The
importance of trans-isolimonene compounds in

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JULIANTO et al., Orient. J. Chem., Vol. 33(6), 3107-3111 (2017)
drugs development not comparable with the Isomerisation of 3-carene to 2-carene
availability in nature, therefore sought other With solvent, xylene
methods for producing trans-isolimonene using
synthesis way.
A total of 15 mg 3-carene included in the
reflux of 500 ml flask along with 15 ml xylene and
.5 g of sodium metal and 0.5 ml of o-chlorotoluene.
0
The mixture refluxed for 12 h, 24 h, and 48 h.
respectively. Furthermore, reflux resulting solution
is cooled to room temperature. The solution was
decanted to separate the catalyst from the solution.
Then the solution was analyzed using Gas
Chromatography – Mass Spectrometer to determine the
12
equilibrium formation of 3-carene and 2-carene .
trans-isolimonene
Without solvent, xylene
Trans-isolimonene can be produced from
A total of 30 ml 3-carene included in the
2
2
3
-carene via thermal isomerization,while compound
-carene was obtained using isomerization of
-carene.The isomerization of 3-carene to 2-carene
reflux of 500 ml flask along with 0.5 g of sodium
metal catalyst and 0.5 ml o-chlorotoluene. The
mixture refluxed for 12, 24, and 48 h. respectively.
Furthermore, reflux resulting solution is cooled to
room temperature. The solution was decanted to
separate the catalyst from the solution. Then the
solution was analyzed using Gas Chromatography–
Mass Spectrometer to determine the equilibrium
formation of 3-carene and 2-carene.
is reported to take place in several methods. Over
hydrogenation catalysts such as Raney nickel and
Pd on carbon, 2-carene was produced in addition
to the hydrogenated products under a hydrogen
atmosphere but the selectivity of this reactions is
7
low because of hydrogenation to carane .
Shimazu, et al., reported that 3-carene undergoes
8
isomerization to 2-carene over solid bases of MgO
RESULT AND DISCUSSION
9
10
and CaO, Ni/SiO catalyst , glaucolite , and basic
2
11
zeolite . All of these previous methods need high
temperature condition and low selectivity of
Influence of solvent free condition on isomerization
-carene to 2-carene
3
2
-carene.
The isomerization of 3-carene to 2-carene
can be done using alkaline catalyst of sodium/
o-chlorotoluene. Reaction between sodium metal
and o-chlorotoluene produces a salt-containing
carbanion act as strong base (Scheme 1).
In this work, we prepared 2-carene from
-carene using Booth’s method .The reaction occur
12
3
at certain temperature with xylene solvent and
catalyst Na/o-chlorotoluene for 1 night. The
existence of xylene solvent requires a separation
process using fractional distillation to separate the
product from the solvent.
In this study, our objective is to understand
the influence of solvent-free isomerization 3-carene
to 2-carene on its conversion and selectivity.
o-chlorotoluene
Scheme. 1
Furthermore, this carbanion take hydrogen
atoms on saturated C-C bond of 3-carene causing
electron rearrangement to form 2-carene isomer
MATERIALS AND METHOD
Materials
(Scheme 2).
Sodium metal, 3-carene, and o-chlorotoluene
were purchased from Merck-Millipore (Germany).
Analysis by using Gas Chromatography-Mass
Spectrometer (GC-MS) Shimadzu QP2100SP with
RTX-5 column.
Reaction mechanism that is catalyzed
olefin isomerization base is closely related to the
chemical nature of the carbanion. Reaction can

JULIANTO et al., Orient. J. Chem., Vol. 33(6), 3107-3111 (2017)
3109
occur in a homogeneous solution system and the
presence of a strong base catalyst. In the previous
study, the solvent xylene used to support the catalyst
basicity. The solvent sufficiently suitable to induce
the formation of carbanion.
170°C the thermodynamic equilibrium between 3-
carene and 2-carene corresponds to a mixture of
60% of 3-carene and 40% of 2-carene.
3
-carene
2-carene
Scheme. 2
This study has been conducted isomerization
of 3-carene to 2-carene without the use of solvent
compared to the isomerization with solvent
condition. Our objective in this study was to avoid
the using solvent in this isomerization reaction.
Fig.1. Showed the results of isomerization reaction
with solvent xylene and without solvent condition.
Both of reactions refluxed for 16 hours.
Fig. 2. Chromatograms of isomerization result of
3-carene refluxed for 24 hours (A) with xylene
solvent (B) without solvent
Figure.3. showed that more time refluxing for
48 h. also gave 2-carene product but at the same time
obtained by-products of m-cymene and p-cymene.
Fig. 1. Chromatograms of isomerization result of
3-carene refluxed for 16 h. (A) with xylene solvent
(
B) without solvent
Refluxing for 16 h did not gave 2-carene
product. It need more time to optimize isomerization
condition. Addition of reflux time have been
observed. Fig.2 demonstrated the result of
isomerization for 24 h of refluxing. Solvent-free
isomerization also gave product of 2-carene as well
as reaction with xylene solvent. At temperature 150-
Fig. 3. Chromatograms of isomerization result of
3-carene refluxed for 48 hours (A) with xylene
solvent (B) without solvent

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JULIANTO et al., Orient. J. Chem., Vol. 33(6), 3107-3111 (2017)
According to previous research, cymene solvent condition. It reinforces previous research
can obtained through dehydrogenation 3-carene that isomerization of 3-carene to 2-carene can also
9
and 2-carene (scheme 3) .
be done without using solvent as well as using
xylene solvent.
These results showed that the isomerization
also occur in solvent-free condition. The optimum
result according to this work is the isomerization for
Fig. 4. Conversion of 3-carene to 2-carene
2
4 h, while the isomerization for 48 h obtained
by-products of cymenes.
Conversion and selectivity of isomerization 3-carene
to 2-carene
Conversion and selectivity were measured
based on amount of chromatograms area. The
conversion of 3-carene (C), selectivity of 2-carene
(
S) are described by the following equations that
[
3c] represents the initial concentration of 3-carene
o
and [3c] and [2c] represent the final concentration
t
t
of 3-carene and 2-carene, respectively.
Fig. 5. Selectivity of 3-carene to 2-carene
CONCLUSION
C = ([3c]o - [3c]t )/[3c]o
S = [2c]t / ([3c]o - [3c]t)
In conclusion, the free solvent isomerization
of 3-carene to 2-carene can be done for 24 h. with
Conversion of 3-carene in both of condition
increased with increasing reaction time (Figure. 4).
27.72% of conversion and 83.27% of selectivity.
The optimum isomerization selectivity of
ACKNOWLEDGMENTS
3
-carene to 2-carene reached when the reaction
conducted in 24 h. refluxing. The selectivity of
isomerization with xylene solvent and isomerization
without solvent are 86.87% and 83.27%,
respectively (Fig.5). There were no significant
differences between xylene solvent and without
This research was financially supported
by Scholarship of Indonesian Directorate of Higher
Education (DIKTI) and Directorate of Research and
Community Service of Islamic University of
Indonesia (UII).
REFERENCES
1.
Beilstein. 1904. J. Russ. Phys. Chem. Soc. 36
in Sutherland, Maurice, D. A. Review of
Densities and Refractive Indices of The 2.
Terpene. Papers. Department of Chemistry,
University of Queensland. 1948, 34(1), 11.
Yadav, J.S., Babu, R.S., and Sabitha, G.Total

JULIANTO et al., Orient. J. Chem., Vol. 33(6), 3107-3111 (2017)
3111
Synthesis of Artemisinin. ARKIVOC, 2003,
, 125.
9.
Lesage, P., Candy, J. P., Hirigoyen, C.,
Humblot, F., Leconte, M., Basset, J. M.,An
example of the valorization of terpenes: The
selective isomerization of 3-carene to 2-
carene in the presence of silica supported
nickel catalysts modified by tetrabutyl tin.J.
Mol. Cat. A: Chemical, 1996, 112, 303-309.
Utenkova, D.B.;Skakovskii, E.D.;Senkov, G.
M.; Agabekov, V. E.; Baranovskii, A. V.;
Bogushevich, S.E.;and.Sidorenko, A.Y.NMR
and GC analysis of 3-carene Isomerization
over Activated Glauconite, Journal of
Spectroscopy, 2017, 83(6), 1026-1030.
Meyer, U., and Hoelderich, W.F. Application
of basic zeolites in the decomposition
reaction of 2-methyl-3-butyn-2-ol and the
isomerization of 3-carene. Journal of
Molecular Catalysis A: Chemical, 1999, 142,
213–222.
3
3
.
.
Lawrence, B.M. Mint-The Genus Mentha:
Medicinal and Aromatic Plant-Industrial
Profile. CRC Press, Boca Raton, 2007, 388.
Bhuiyan, M.N.I.; Begum, J.;Sardar, P.K.; and
Rahman, M.S.;Constituents of Peel and Leaf
Essential Oils of Citrus medica L. J.Sci.Res.,
4
10.
11.
12.
2
009, 1(2) 387-392.
5
.
.
Meena A.K.; Kandale Ajit; Rao A.M.A Review on
Citron-Pharmacognosy, Phytochemistry and
Medicinal Uses. IRJP, 2011, 2 (1), 14-19.
Fayed, S. A. Antioxidant and Anticancer
Activities of Citrus reticulate (Petitgrain
Mandarin) andPelargonium graveolens
6
(Geranium) Essential Oils.Res. J. Agric. & Biol.
Sci., 2009, 5(5), 740-747.
7
.
.
Basset, J. M. Modern Surface Organo metallic
Chemistry, Wiley-VCH, Weinheim, 2006, 124.
Shimazu, K.;Hattori, H;Tanabe, K.Isomerization
of 3-carene over MgO and CaO, Journal of
Catalysis. 1977, 48, 302-311.
8
Booth, A. B. and Island, J. 8-halo-2-menthene
and its method of preparation. United States
Patent Office, August, 1973, 2, 3755472.