Solvent-free Isomerization of 3-carene to 2-carene using Na/o-chlorotoluene Catalyst in trans-isolimonene Production

Introduction

Trans-isolimonene is one of monoterpenoid compounds that a rare and little-studied substance. It was first synthesized by Tshugaev in 1903 ¹. Now trans-isolimonene may become a fully accessible monoterpenoid use as one of starting material for some drug compounds development such as in synthesis of antimalarial drug artemisinin ² and synthesis of menthol ³. This compound is rarely found naturally in plants. Several studies have reported that isolimonene found in essential oils of Citrus medica and Citrus reticulate.  The peel oil of Citrus medica contain isolimonene about 39.37% ^4,5 and 5.87% in Citrus reticulate essential oil ⁶. The importance of trans-isolimonene compounds in drugs development not comparable with the availability in nature, therefore sought other methods for producing trans-isolimonene using synthesis way.

Trans-isolimonene can be produced from 2-carene via thermal isomerization, while compound 2-carene was obtained using isomerization of 3-carene. The isomerization of 3-carene to 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 low because of hydrogenation to carane ⁷. Shimazu, et al. ⁸ reported that 3-carene undergoes isomerization to 2-carene over solid bases of MgO and CaO, Ni/SiO₂ catalyst ⁹, glaucolite ¹⁰, and basic zeolite ¹¹. All of these previous methods need high temperature condition and low selectivity of 2-carene.

In this work, we prepared 2-carene from 3-carene using Booth’s method ¹². The reaction occur 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.

Materials and Method

Materials

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.

Isomerisation of 3-carene to 2-carene

With Solvent of Xylene

A total of 15 mg 3-carene included in the reflux of 500 mL flask along with 15 mL xylene and 0.5 g of sodium metal and 0.5 mL of o-chlorotoluene. The mixture refluxed for 12 hours, 24 hours, and 48 hours 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 ¹².

Without Solvent of Xylene

A total of 30 mL 3-carene included in the 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 hours 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.

Result and Discussion

Influence of Solvent free Condition on Isomerization 3-carene to 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).

Scheme 1 Click here to View scheme

Furthermore, this carbanion take hydrogen atoms on saturated C-C bond of 3-carene causing electron rearrangement to form 2-carene isomer (Scheme 2).

Scheme 2 Click here to View scheme

 

Reaction mechanism that is catalyzed olefin isomerization base is closely related to the chemical nature of the carbanion. Reaction can 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.

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. Figure 1 showed the results of isomerization reaction with solvent xylene and without solvent condition. Both of reactions refluxed for 16 hours.

Figure 1: Chromatograms of isomerization result of 3-carene refluxed for 16 hours (A) with xylene solvent (B) without solvent Click here to View figure

 

Refluxing for 16 hours did not gave 2-carene product. It need more time to optimize isomerization condition. Addition of reflux time have been observed. Figure 2 demonstrated the result of isomerization for 24 hours of refluxing. Solvent-free isomerization also gave product of 2-carene as well as reaction with xylene solvent. At temperature 150-170°C the thermodynamic equilibrium between 3-carene and 2-carene corresponds to a mixture of 60% of 3-carene and 40% of 2-carene.

Figure 2: Chromatograms of isomerization result of 3-carene refluxed for 24 hours (A) with xylene solvent  (B) without solvent Click here to View figure

 

Figure 3 showed that more time refluxing for 48 hours also gave 2-carene product but at the same time obtained by-products of m-cymene and p-cymene.

Figure 3: Chromatograms of isomerization result of 3-carene refluxed for 48 hours (A) with xylene solvent (B) without solvent Click here to View figure

According to previous research, cymene can obtained through dehydrogenation 3-carene and 2-carene (scheme 3) ⁹.

Scheme 3 Click here to View scheme

 

These results showed that the isomerization also occur in solvent-free condition. The optimum result according to this work is the isomerization for 24 hours, while the isomerization for 48 hours 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]_o represents the initial concentration of 3-carene and [3c]_t and [2c]_t represent the final concentration  of 3-carene and 2-carene, respectively.

C = ([3c]_o – [3c]_t )/[3c]_o

S = [2c]_t /  ([3c]_o – [3c]_t)

Conversion of 3-carene in both of condition increased with increasing reaction time (Figure 4).

Figure 4: Conversion of 3-carene to 2-carene Click here to View fgiure

 

The optimum isomerization selectivity of 3-carene to 2-carene reached when the reaction conducted in 24 hours refluxing. The selectivity of isomerization with xylene solvent and isomerization without solvent are 86.87% and 83.27%, respectively (Figure 5). There were no significant differences between xylene solvent and without solvent condition. It reinforces previous research that isomerization of 3-carene to 2-carene can also be done without using solvent as well as using xylene solvent.

Figure 5: Selectivity of 3-carene to 2-carene Click here to View figure

 

Conclusion

In conclusion, the free solvent isomerization of 3-carene to 2-carene can be done for 24 hours with 27.72% of conversion and 83.27% of selectivity.

Acknowledgments

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).

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