Regioselective Synthesis of Monoepoxides from Terpenic Diolefins

Ind. Eng. Chem. Res. 2009, 48, 4671–4680

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Regioselective Synthesis of Monoepoxides from Terpenic Diolefins over Alumina at High Temperature and Pressure Marıá A. Uguina,*,† Jose´ A. Delgado,† Jose´ Carretero,† Diego Go´mez-Dıáz,‡ and Goretti Rodrı´guez† Department of Chemical Engineering, Faculty of Chemistry, Complutense UniVersity of Madrid, 28040 Madrid, Spain, and Department of Chemical Engineering, Higher Technical Engineering School, UniVersity of Santiago de Compostela, 15782 A Corunã, Spain

Alumina is a heterogeneous catalyst for the regioselective epoxidation of terpenic diolefins that deactivates in presence of water. The reactions can be carried out at high temperature, above the boiling point of the solvent, increasing the pressure to maintain the reaction mixture in the liquid phase, yielding conversions between 41% and 96% and selectivities between 19% and 75% to monoepoxides with a significant decrease of reaction times. Deactivated alumina was analyzed, and an effective regeneration method was proposed. Furthermore, to improve the monoepoxide productivity, the effects of temperature, pressure, stirring rate, water concentration, alumina loading, and reactive concentrations were studied. 1. Introduction Recently, the selective and efficient epoxidation of alkenes has been the subject of considerable investigation, because the resulting epoxides are versatile intermediates in various organic syntheses for manufacturing a great variety of important commercial products.1 There is also interest in the development of new effective stable catalysts in the context of green chemistry,2 which reduces the amount of byproducts and the environmental impact of the synthesis process, using nonpolluting solvents and hydrogen peroxide as the oxidant, because it is relatively cheap and gives water as the only byproduct. Several reviews have been published on this subject, focusing on the immobilization of active metals on different supports. However, the heterogenization of homogeneous catalysts has had limited success because of their poor stability, which leads to leaching of the active metal during the reaction.3–6 In the recent literature there are several reports on the epoxidation of limonene, a terpenic diolefin, using catalysts such as Ti-MCM-41,7 titanium-silica,8 silicates containing molybdenum,9 supported Keggin heteropolycompounds,10 and hydrotalcite-like compounds in the presence of nitriles,11 giving good to high yields. Alumina has been widely used as a catalyst or as a support for active metals in the production of fine chemicals.12 The use of transition-metal-free alumina in the epoxidation of alkenes with hydrogen peroxide was reported in the 1970s,13 but low yields were obtained and large excesses of both alumina and hydrogen peroxide were used. In the past few years, several articles have been published showing the catalytic properties of different kinds of alumina (boehmite and γ-, δ- and θ-Al2O3),14,15 as used in the epoxidation of several alkenes,16–18 terpenes,17,19 and unsaturated fatty esters20 in an anhydrous or low-water-content medium with ethyl acetate as the solvent. High conversions and selectivities to epoxides were obtained. The presence of water led to the deactivation of the alumina.16–18 Hydrogen peroxide can also be activated in the absence of a transition metal. Highly halogenated ketones21 and organic derivatives of arylselenium acids22 react with H2O2 to form * To whom correspondence should be addressed. Tel.: +34 913944113. Fax: +34 913944114. E-mail: [email protected]. † Complutense University of Madrid. ‡ University of Santiago de Compostela.

different activated species that are able to epoxidate alkenes. However, these systems require contaminant solvents such as fluorinated alcohols or dichloroethane to obtain high yields. Other compounds for activating hydrogen peroxide are described in the literature: (i) carbodiimide with mildly basic or acidic catalyst23 and (ii) hydrogen carbonate ion, which forms the active oxidant peroxomonocarbonate ion.24 In a previous work,25 we reported the regioselective epoxidation of different terpenes over γ-Al2O3 at atmospheric pressure and temperature below the boiling point of the solvent, including reuse of the catalyst. The deactivation of the alumina, studied with two substrates with high and low reactivities (terpinolene and limonene, respectively), was clearly observed only with the least reactive one (limonene), which required a long reaction time to reach high conversion (78% at 72 h). In this work, the deactivation of the alumina was analyzed, and an effective regeneration method is proposed. Furthermore, the activity and selectivity of alumina in the regioselective synthesis of monoepoxides from terpenes (carvone, limonene, terpinolene, and γ-terpinene) at high temperature and pressure was analyzed, so as to reduce the reaction times and enhance the productivity of monoepoxides. 2. Experimental Section Chromatographic basic alumina was supplied by Aldrich (type 507C). Its textural properties were determined by nitrogen adsorption analysis at 77 K (Micrometrics ASAP 2010). The BET (Brunauer-Emmett-Teller) surface area was 162 m2 · g-1, and the pore volume and average pore diameter were 0.26 cm3 · g-1 and 0.52 nm, respectively, both estimated by the BJH (Barrett-Joyner-Halenda) method. The XRD spectra of this material showed that it is of the γ type. Diffuse reflectance Fourier transform infrared (DRIFT) spectra were recorded under a vacuum using 64 scans between 400-4000 cm-1 with a resolution of 4 cm-1 on a ThermoNicolet 360 spectrometer, equipped with a Spectra-Tech diffusereflectance high-temperature vacuum chamber with KBr windows. γ-Alumina was ground into a fine powder with an agate mortar and transferred into an aluminum sample cup. The samples were first dehydrated at 400 °C for 1 h under a vacuum and then cooled to room temperature.

10.1021/ie801763e CCC: $40.75  2009 American Chemical Society Published on Web 04/02/2009

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Ind. Eng. Chem. Res., Vol. 48, No. 10, 2009

Figure 1. Substrates and their respective monoepoxides and diepoxides.

Carvone (5-isopropenyl-2-methyl-2-cyclohexenone, 98%), limonene (4-isopropenyl-1-methyl-1-cyclohexene, 99%), and γ-terpinene (1-isopropyl-4-methyl-1,4-cyclohexadien, 97%) were supplied by Aldrich. Terpinolene (4-isopropylidene-1-methylcyclohexene, 85%) was supplied by Fluka. All of the substrates were used without further purification. The substrates and their respective mono- and diepoxides are shown in Figure 1. Solutions of anhydrous hydrogen peroxide in dry ethyl acetate were prepared by liquid-liquid extraction from a commercial hydrogen peroxide aqueous solution (Aldrich, 50% w/w), with the water removed from the organic phase using anhydrous sodium sulfate as a desiccant. The hydrogen peroxide concentration in ethyl acetate solution was determined by mixing a sample (previously diluted with water) with TiOSO4 and measuring the resulting yellow peroxo complex concentration by UV-vis spectrophotometry.26 The mean hydrogen peroxide concentration in ethyl acetate obtained by this method was 10% (w/w). All analyses were repeated once, giving a standard deviation of about 2-3%, which is lower than that obtained with classical methods such as iodometric titration (6-7%). In a typical experiment at high temperature and pressure, 0.18 g of alumina (previously dried at 110 °C) was added to a mixture of 7 mmol of substrate, 14 mmol of hydrogen peroxide (∼10% in ethyl acetate), and 22 mL of dry ethyl acetate (so that the substrate/H2O2/Al2O3 molar ratio was 4:8:1). The reaction time was 8 h. A Teflon vessel inside an autoclave stainless steel reactor, with a Teflon paddle stirrer, was used, which allowed (i) the reaction to be performed without reflux; (ii) the experiments to be carried out at temperatures higher than the mixture boiling point (up to 140 °C), by increasing the pressure to maintain the reaction mixture in the liquid phase; and (iii) peroxide decomposition by reaction with steel walls to be prevented. To achieve the required pressure, this reactor had a valve to regulate the flow of nitrogen, a manometer to measure the inside pressure, and another valve to reduce the pressure to atmospheric. Before this valve can be opened, the temperature inside must be reduced to room temperature to prevent the liquid mixture from evaporating. The final conversion and selectivity were measured by taking samples from the reaction mixture and analyzing them by gas chromatographymass spectrometry (GC-MS; Agilent Technologies 6890N GC equipped with a J&W DB-23 capillary column and a 5973N mass-selective detector). The consumption of hydrogen peroxide was measured using the method described previously. The alumina reuse tests were carried out in a magnetically stirred two-neck vessel fitted with a reflux condenser and heated in an oil bath at 60 °C. The exact measurement of the stirring rate was not possible because of the experimental equipment employed, so a maximum value of this variable was selected

(>1000 rpm). According to previous results,25 the reaction rate was not controlled by external mass-transfer resistance under these conditions. In these experiments, 0.25 g of the catalyst was used, keeping the same proportion of catalyst, substrate, oxidant, and solvent as in the experiments at high temperature. To regenerate the catalyst, 0.3 g of Al2O3 was added to 3 mL of NaOH 1% w/w, stirred for 100 min at room temperature, washed with distilled water until neutral pH was obtained, and dried at 110 °C overnight. Several parameters were calculated to evaluate the catalyst performance, defined as follows (all amounts of compounds in these equations are expressed in millimoles):

(

conversion (%) ) 100 × 1 -

remaining diolefin initial diolefin

)

(1)

monoepoxide (2) ( initial diolefin ) remaining peroxide H O consumption (%) ) 100 × (1 initial peroxide ) yield (%) ) 100 ×

2

2

(3) product selectivity (%) ) 100 × H2O2 efficiency (%) ) 100 ×

(

[∑

desired product (products)

]

mmol of epoxides mmol of H2O2 consumed

(4)

)

(5)

3. Results and Discussion 3.1. Catalyst Regeneration. In a previous work,25 we studied the deactivation of alumina at atmospheric pressure and temperature below the boiling point of the solvent, with two substrates with high and low reactivities (terpinolene and limonene, respectively) at two different reaction times (8 and 72 h). Deactivation was clearly observed only with the least reactive substrate (limonene), which required a long reaction time (72 h) to reach high conversion. In this article, we present an effective regeneration method for reusing alumina after the epoxidation of limonene. Figure 2 shows the results of limonene epoxidation catalyzed by (a) fresh alumina, (b,c) alumina reused one and two times, and (d) alumina regenerated after the first reuse. It can be observed that, after the first use, the alumina loses 40% of its activity, maintaining a constant selectivity to endocyclic monoepoxide (IL). Further deactivation was not observed during the second reuse of the catalyst. To regenerate the alumina, it was proposed to wash it with diluted NaOH, following a method similar to that used in chromatographic


Figure 2. Effect of successive reuses and regeneration of alumina on the epoxidation of limonene. Reaction conditions: 10 mmol of substrate, 20 mmol of H2O2, 30 mL of AcOEt, 0.25 g of Al2O3, 60 °C, 72 h. (Black bars) conversion, (white bars) selectivity to endocyclic monoepoxide (IL). (a) Fresh, (b) first reuse, (c) second reuse, (d) regenerated after first reuse.

Figure 3. DRIFT spectra of aluminas: (a) fresh, (b) after first use, (c) after second use, (d) after second use and treatment with NaOH.

separations with alumina. It was observed that the alumina recovers its initial activity with this procedure (see Experimental Section). The DRIFT spectra in the hydroxyl stretching region of fresh, used, and NaOH-treated aluminas are shown in Figure 3. A significant decrease of the broad peak in the range 3550-3650 cm-1 is observed for the used sample. However, when this alumina is treated with NaOH after the second use, the peak recovers its initial intensity. Therefore, it is reasonable to relate the loss of alumina activity to the decrease of this peak. A tentative hypothesis for the regeneration of alumina with this method is that the adsorbed compounds are removed by this treatment, restoring the OH groups covered by these compounds. In Figure 4, thermogravimetric (TG) analysis shows that alumina adsorbs compounds after one use (thermally desorbed between 150-550 °C). However, alumina treated with dilute NaOH after the second use loses these compounds, and only retains compounds adsorbed with high strength (thermally desorbed between 450-550 °C) that seem not to contribute to alumina catalytic activity. The assignment of the OH spectrum of transition aluminas has been a controversial task for the past four decades. During this time, four models of surface hydroxyl species have been proposed to explain the multiplicity of bands,27,28 where the models proposed by Kno¨zinger and Ratnasamy29 and by Busca et al.30,31 are the most employed ones. Both models divide the surface OH groups of alumina into five groups (Figure 5). However, there is no agreement about the assignment of the broad peak in the range of 3550-3650 cm-1. This peak can be assigned to H-bonded hydroxyls, according to the Kno¨zinger

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Figure 4. TG analysis of aluminas: (s) fresh, (- - -) after first use, ( · · · ) after second use and treatment with NaOH.

and Ratnasamy’s model or to tribridged hydroxyls according to Busca et al.’s model. 3.2. Epoxidation Reactions at High Temperature and Pressure. Table 1 lists the catalytic activities of alumina in the epoxidations of carvone, limonene, terpinolene, and γ-terpinene at 100 °C. Conversion values of the different terpenes, which are indicative of their reactivity, increase with the number of substituents of the two double bonds in each molecule (excluding the substituent of the R,β-unsaturated ketone group of carvone, which is an electron-deficient alkene because of the effect of carbonyl group), as was observed at lower temperatures,25 except for γ-terpinene. The conversion of this substrate is higher than that of terpinolene, despite its lower number of substituents. This is attributed to the fact that the increase with temperature of the rate of secondary reactions giving p-cymene is higher for γ-terpinene, because the two double bonds of this molecule are located within the six-membered ring, which favors the formation of benzene derivatives such as p-cymene. For carvone, the reactivity of the endocyclic double bond is quite low because of the electronic-withdrawing effect of the ketone group conjugated with this double bond, giving the exocyclic monoepoxide (IIC) as the main product by means of a regiospecific epoxidation. The regioselectivity observed in the epoxidations of limonene and terpinolene also depends on the effect of the number of substituents in each double bond present in the molecule. For limonene, the endocyclic monoepoxide (IL) is the most formed product, which comes from the epoxidation of the more substituted double bond. The same applies to the exocyclic monoepoxide of terpinolene (IIT). For γ-terpinene, the epoxidation did not show regioselectivity, and the selectivities to the various monoepoxides are similar, because the two double bonds of this substrate have the same number of substituents. In this case, a significant amount of p-cymene is obtained as a byproduct, which is probably produced by oxidative dehydrogenation reactions involving the internal double bonds in the six-membered ring.32 The selectivities to monoepoxides from some terpenes (limonene, citronelal, citral, citronelol, and R-pinene) in their epoxidation with H2O2 over alumina have been reported elsewhere, with the regioselectivity of these epoxidations explained theoretically by DFT molecular orbital calculations.33 Despite the different reaction conditions, the selectivity to the endocyclic monoepoxide of limonene (IL) obtained in this work is similar to that reported in the literature (77% vs 80%). 3.3. Effect of Temperature. To study the effect of this variable, a set of experiments was carried out varying the temperature from 60 to 140 °C, with the pressure set to 20 atm

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Figure 5. Surface hydroxyl groups on alumina and spectral positions proposed by (A) Kno¨zinger and Ratnasamy’s model and (B) Busca et al.’s model (0 ) cation vacancy). Table 1. Catalytic Activity of Alumina in the Epoxidation of Terpenic Diolefinsa selectivity (%) substrate carvone limonene terpinolene γ-terpinene

conversion (%) 41.5 74.2 89.9 95.9

I 14.2 77.1 2.5 20.7

H2O2

II

III

p-cymene

74.7 7.7 72.4 19.0

10.0 6.6 13.1

4.1 43.3

others b

11.1 5.2b 14.4c 3.9d

consumption (%)

efficiency (%)

70 87 77 72

26 45 51 44

a Reaction conditions: 7 mmol of substrate, 14 mmol of H2O2, 22 mL of AcOEt, 0.18 g of Al2O3, 700 rpm, 100 °C, 8 h, 20 atm. b Several products unidentified. c Carvone, carveol, dihydrocarvone and others unidentified. d p-Cymen-8-ol and others unidentified.

Figure 6. Effect of temperature on the catalytic activity of alumina in the epoxidation of carvone and limonene. Reaction conditions: 7 mmol of substrate, 14 mmol of H2O2, 22 mL of AcOEt, 0.18 g of Al2O3, 20 atm, 60-140 °C, 700 rpm, 8 h. (a) Effect on conversion: (black bars) carvone, (white bars) limonene. (b) Effect on selectivity: (() IC, (]) IL, (9) IIC, (0) IIL.

with N2 to avoid solvent evaporation. The influence of reaction temperature on the conversion reached for carvone and limonene is show in Figure 6. An increase in reaction temperature to 120 °C produces an increase in the substrate conversion (Figure 6a), whereas the conversions at 120 and 140 °C are quite similar. This result is due to the complete consumption of hydrogen peroxide at high temperature by (i) the reaction to produce oxygenated products and (ii) the decomposition of hydrogen peroxide into water and oxygen. The epoxide selectivity to the most formed species (IIC and IL) decreases as the reaction temperature increases, because of secondary reactions that result in the opening of the oxirane ring yielding ketones, aldehydes, and hydroxyl and diol groups. The amounts of these byproducts are much lower when the epoxidation is performed at low temperatures (Figure 6b). For carvone, the variation in the selectivity to monoepoxides (IC and IIC) with temperature indicates that the rate of formation

of the epoxide coming from the least nucleofilic double bond (IC) increases faster with this variable, suggesting that the activation energy of IC monoepoxide formation is higher. Unlike carvone, the decrease in selectivity to the IL monoepoxide (the most formed product from limonene) is due to its higher decomposition rate, which results in a higher formation of byproducts. Temperature did not affect the H2O2 efficiency when the reaction was performed in the experimental setup with high pressure. Table 2 shows a comparison of the experimental results obtained at 60 °C and atmospheric pressure21 with those obtained at 100 °C and 20 atm. It must be noted that the results at 60 °C were obtained in a different reactor, with a higher degree of mixing (magnetic stirring). It can be observed that the carvone conversion at 100 °C is higher than that at 60 °C, despite the fact that it is reached in a much shorter time (8 vs 72 h), without a significant variation


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a

Table 2. Catalytic Activity of Alumina in the Epoxidation of Carvone and Limonene with Two Different Sets of Reaction Conditions selectivity (%)

c

H2O2

substrate

conversion (%)

yieldd (%)

I

II

III

others

consumption (%)

efficiency (%)

carvoneb carvonec limoneneb limonenec

32.5 41.5 77.6 74.2

31.0 31.0 62.9 57.2

2.4 14.2 81.0 77.1

95.4 74.7 6.5 7.7

9.4 10.0

2.2 11.1 3.1 5.2

30 70 61 87

52 26 68 45

a Reaction conditions: 7 mmol of substrate, 14 mmol of H2O2, 22 mL of AcOEt, 0.18 g of Al2O3, 700 rpm. Conditions: 100 °C, 8 h, 20 atm. d Yield of IIC or IL.

in the yield of the most formed monoepoxide (IIC). For limonene, which is more reactive than carvone, the conversion and yield decrease slightly at 100 °C. This can be attributed to the higher consumption of hydrogen peroxide, indicating that the rate of epoxidation of this substrate is less affected by temperature, probably because the activation energy of epoxidation is lower. A decrease in selectivity with temperature was also observed. The hydrogen peroxide efficiency for both substrates was lower at 100 °C because of the loss of selectivity to the monoepoxides (see eq 5) and the increase in the decomposition of H2O2. Taking into account the opposite effect of temperature on substrate conversion and selectivity, the rest of the experiments were performed at 100 °C, because of the significant increase in conversion and the low decrease in selectivity at this temperature, compared with the results obtained at 60 °C. Kinetic Study of the Epoxidation of Carvone and Limonene over Alumina. The activation energies of the epoxidations of carvone and limonene over alumina were estimated from the experimental results obtained at different temperatures. Because of the autoclave used in these reactions, samples at intermediate reaction times could not be taken, so reaction rates were estimated using the conversion values at the end of the reaction. The results obtained in the experiments at 120 and 140 °C were discarded, because the global reaction rate was limited by the almost complete consumption of hydrogen peroxide. The following second-order kinetic equation for heterogeneous systems was employed to calculate the reaction rate34 nΑ2 1 dnΑ ) -kCΑ2 ) -k 2 W dt V

(6)

where nA is the number of moles of substrate, W is the catalyst weight, V is the liquid volume, k is the kinetic rate constant, and t is the time. Integrating eq 6 gives the function nA(t) as 1 1 kW )- 2 t nΑ nΑ0 V

(7)

where nA0 is the initial value of nA. A set of experiments was carried out at 60 °C and atmospheric pressure with different alumina loadings for limonene and carvone in the experimental setup used in a previous work,25 which allows samples to be taken at different times. Figure 7 shows a plot of 1/nA vs time for these experiments. The experimental data could be fitted with eq 7 quite well, confirming the validity of second-order kinetics for both substrates. Preliminary tests with other reaction orders (n ) 0, 1) resulted in a poorer fitting quality. The kinetic rate constants derived from this calculation are reported in Table 3. These data could be fitted adequately with the Arrhenius equation, k ) A exp(-EA/RT), as can be observed in Figure 8. From these results, activation energies (EA) of 66.7 and 61.7 kJ · mol-1 and pre-exponential factors (A) of 31.3 and 25.7

b

Conditions: 60 °C, 72 h, 1 atm.

Figure 7. Plot of 1/nA vs time for the epoxidation of limonene and carvone over alumina. Reaction conditions: 10 mmol of substrate, 20 mmol of H2O2, 30.3 mL of AcOEt, 0.125-0.330 g of Al2O3, 60 °C, 72 h, substrate/Al2O3 molar ratio: (]) 0.125, (0) 0.25, and (O) 0.33 for limonene and (9) 0.25 for carvone. Table 3. Kinetic Rate Constants (k, m6 · kg-1 · s-1 · mol-1) in the Epoxidation of Terpenes over Alumina substrate carvone limonene

60 °C

80 °C -9

1.13× × 10 5.59 × 10-9

100 °C -9

4.05 × 10 20 × 10-9

14.9 × 10-9 60.7 × 10-9

m6 · kg-1 · s-1 · mol-1 were obtained for carvone and limonene, respectively. The lower activation energy of limonene indicates that this substrate is more reactive than carvone. 3.4. Effect of Pressure. The influence of reaction pressure on the epoxidation of limonene (above the pressure needed to maintain the reaction mixture in the liquid phase) was studied in the range of 4-40 atm. Pressure showed a negligible effect on conversion, epoxide selectivity, and hydrogen peroxide efficiency (Figure 9), as expected for a reaction in the liquid phase. 3.5. Effect of Stirring. Figure 10 shows the influence of the stirring rate on limonene epoxidation. The results indicate that this variable has a high influence on conversion for lower values

Figure 8. Arrhenius plot of the kinetic rate constant for the epoxidation of terpenes over alumina: (9) carvone, (0) limonene.

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Figure 9. Effect of pressure on the catalytic activity of alumina in the epoxidation of limonene. Reaction conditions: 7 mmol of substrate, 14 mmol of H2O2, 22 mL of AcOEt, 0.18 g of Al2O3, 4-40 atm, 100 °C, 700 rpm, 8 h.

Figure 10. Effect of stirring rate on the catalytic activity of alumina in the epoxidation of limonene. Reaction conditions: 7 mmol of substrate, 14 mmol of H2O2, 22 mL of AcOEt, 0.18 g of Al2O3, 20 atm, 100 °C, 100-1100 rpm, 8 h.

of the stirring rate (100-500 rpm). The increase of conversion with this variable indicates that the mass-transfer resistance across the laminar film around the particles is significant under these conditions. At higher values of the stirring rate (700-1100 rpm), the external mass-transfer resistance is no longer controlling. The epoxide selectivity is not affected by the stirring rate, remaining constant in all of the experiments. The hydrogen peroxide efficiency decreases slightly at low stirring rates, because the amount of substrate that reaches the internal surface of the alumina under these conditions is low, favoring the decomposition of the active sites, according to the complete mechanism reaction reported elsewhere.25 The effect of the internal diffusion resistance was also studied, through the estimation of the so-called Thiele modulus, Φ, which relates the surface reaction rate to the internal diffusion Φ2 )

kCΑ0n-1Fpr2 De

(8)

where k is the kinetic rate constant, CA0 is the initial substrate concentration, Fp is the particle density, n is the reaction order, r is the particle radius, and De is the effective diffusion coefficient. When the Thiele modulus is higher than 0.4, internal diffusion is considered to control the global reaction rate, whereas when Φ is lower than this value, the surface reaction is the limiting step of the process.34 The effective diffusion coefficient, De, was estimated by the equation De )

DABε τ

(9)

where ε is the particle porosity and τ is the tortuosity. In addition, the molecular diffusion coefficient, DAB, was estimated by the Wilke-Chang method, resulting in values of 7.72 × 10-10 and 7.12 × 10-10 m2 · s-1 for limonene and carvone, respectively. The particle porosity and particle density of alumina were measured by mercury porosimetry, resulting in 0.58 and 1043 kg · m-3, respectively. A tortuosity value of 4 was assumed, as this parameter commonly ranges between 2 and 6.35 The particle radius was 0.052 mm, estimated from the average particle diameter. The Thiele modulus values estimated in experiments conducted at 100 °C and 700 rpm for carvone and limonene were 0.12 and 0.24, respectively, indicating the internal diffusion resistance does not control the global reaction rate. This value is higher for limonene than for carvone because the former substrate is more reactive, so its reaction rate is higher. As terpinolene and γ-terpinene are the most reactive substrates, it is expected that their Thiele moduli will be higher still, and the process could be controlled by internal mass transport in those cases. From these results, it was deduced that a stirring rate of 700 rpm is suitable for carrying out the rest of the experiments without the interference of the external and internal mass-transfer resistance. 3.6. Effect of Water. In a previous work,25 it was observed that the concentration of water in the reaction medium, which is formed by H2O2 decomposition, has a significant effect on conversion and selectivity in the epoxidation of terpenes. The effect of water on the epoxidations of different terpenes carried out at high temperature and pressure is shown in Figure 11. The water concentration was varied by adding different amounts of this compound. Figure 11a shows that low quantities of water produce a slight decrease in conversion and epoxide selectivity, without affecting the hydrogen peroxide efficiency. This behavior is due to the hydrophilic character of alumina, which adsorbs water that blocks the active sites, thereby reducing its catalytic activity.17 The negative influence of water depends on the substrate employed, the decrease of alumina activity being higher for the less reactive substrates (carvone > limonene > terpinolene > γ-terpinene), as can be observed in Figure 11b. 3.7. Effect of Alumina Loading. The influence of alumina loading on the epoxidation reaction of γ-terpinene at high temperature and pressure is shown in Figure 12. This substrate was selected for this study because the effect of alumina loading on the epoxidation of the other substrates (carvone, limonene, and terpinolene) has been studied elsewhere.25 It is observed that, in the range studied, an increase of alumina produces an improvement in substrate conversion (Figure 12a). The hydrogen peroxide efficiency initially increases with the alumina loading, reaches a maximum value, and then decreases for Al2O3/ substrate molar ratios higher than 0.33. This characteristic behavior is explained on the basis of two opposite effects: (i) an improvement in the epoxide selectivity when the alumina loading is increased, producing an enhancement in the hydrogen peroxide efficiency, and (ii) a higher decomposition of active sites as a result of the reaction between alumina and hydrogen peroxide. The obtained yield of monoepoxides (IG + IIG) also passes through a maximum (Figure 12a) as a result of two effects: (i) an increase in epoxide selectivity with alumina loading and (ii) a decrease in the selectivity to monoepoxides due to the formation of the corresponding diepoxide (Figure 12b).


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Figure 11. Effect of water on the catalytic activity of alumina in the epoxidation of terpenes. Reaction conditions: 7 mmol of substrate, 14 mmol of H2O2, 0-21 mmol of H2O, 22 mL of AcOEt, 0.18 g of Al2O3, 20 atm, 100 °C, 700 rpm, 8 h. (a) Effect of water on the epoxidation of terpinolene: (black bars) conversion, (white bars) selectivity to all epoxides, (gray bars) H2O2 efficiency. (b) Effect of water on the conversion of different terpenes: (black bars) without water, (white bars) with 21 mmol of water.

Figure 12. Effect of alumina loading on the epoxidation of γ-terpinene. Reaction conditions: 7 mmol of substrate, 14 mmol of H2O2, 22 mL of AcOEt, 0-0.36 g of Al2O3, 20 atm, 100 °C, 700 rpm, 8 h. (a) Effect of loading of Al2O3: (0) conversion, (O) yield of IG + IIG, (() H2O2 efficiency. (b) Effect on selectivity: (9) IG + IIG, (() IIIG, (0) p-cymene, (O) other byproducts.

A significant conversion value was obtained when epoxidation was carried out without alumina (about 35%), but with negligible selectivity to the epoxides of γ-terpinene, the only product being p-cymene. Accordingly, the yield of monoepoxides and the hydrogen peroxide efficiency were very low. These results demonstrate that alumina is a catalyst for this reaction, favoring the production of epoxides. The selectivity to p-cymene is reduced when the amount of alumina is increased, and the production of mono- and diepoxides is improved (Figure 12b). There is a maximum value of p-cymene yield (58%) for an Al2O3/substrate molar ratio of 0.083. 3.8. Optimization of the H2O2/Substrate Molar Ratio. The experimental results reported in the previous sections indicate that, to optimize the yield of monoepoxide for limonene, terpinolene, and γ-terpinene, the peroxide concentration must be controlled in order to avoid the diepoxide production, although the final substrate conversion will be reduced. Figure 13 shows the results obtained by varying the H2O2/ substrate ratio for limonene, terpinolene, and γ-terpinene. It shows that the higher the oxidant concentration, the higher the conversion (Figure 13a). Simultaneously, a decrease in the selectivity to monoepoxide is observed, because of both a higher amount of water in the reaction medium coming from the hydrogen peroxide decomposition and a higher production of diepoxide (Figure 13b). The combination of these two opposite effects results in the presence of a maximum value of monoepoxide yield with the H2O2/substrate ratio (Figure 13c). The performance parameters corresponding to this maximum are given in Table 4.

Finally, Figure 13d shows that the hydrogen peroxide efficiency decreases with the H2O2/substrate ratio, which is attributed to the fact that the number of active sites increases with this variable, so that more active sites go through a decomposition process without reacting with the substrate. For carvone, the optimization method discussed above is not applicable, because the amount of diepoxide obtained in this case is very low as a result of the low reactivity of the R,βunsaturated ketone group. Therefore, for this substrate, it is better to work with a high excess of hydrogen peroxide to increase the yield of the most formed monoepoxide (IIC) without an excessive loss of selectivity. Table 5 shows the effect of increasing the hydrogen peroxide concentration and the reaction time on the performance parameters for the epoxidation of carvone. It is observed that an increase in these variables produces a significant improvement in the conversion and yield of carvone exocyclic monoepoxide (IIC), with the effect of the hydrogen peroxide concentration being higher than that of the reaction time. A negligible decrease in hydrogen peroxide efficiency and a slight decrease in selectivity (about 3%) are also observed. 3.9. Effect of Reactant Concentrations. Table 6 shows the effect of the reactant concentrations (substrate and hydrogen peroxide) on the epoxidation of limonene. It is observed that, when this variable is increased by a factor of 4 (from 0.25 to 1 M), the conversion and the hydrogen peroxide efficiency decrease noticeably. Likewise, the selectivity to all of the epoxides is reduced because of the higher formation of byproducts. This is attributed to the higher amount of water formed

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Figure 13. Effect of H2O2/substrate molar ratio on the epoxidation of terpenes. Reaction conditions: 7 mmol of substrate, 7-21 mmol of H2O2, 22 mL of AcOEt, 0.36 g of Al2O3, 20 atm, 100 °C, 700 rpm, 8 h. (a) Effect on conversion: (0) γ-terpinene, (O) limonene, (() terpinolene. (b) Effect on selectivity: (0) IG + IIG, (O) IL, (() IIT, (9) IIIG, (b) IIIL, (]) IIIT. (c) Effect on yield: (0) IG + IIG, (O) IL, (() IIT. (d) Effect on H2O2 efficiency: (0) γ-terpinene, (O) limonene, (() terpinolene. Table 4. Epoxidation of Terpenes at the Optimum H2O2/Substrate Molar Ratioa selectivity (%) substrate

H2O2/substrate

conversion (%)

yieldb (%)

I

II

III

others

limonene γ-terpinene terpinolene

2 1.2 1.75

86.4 88.4 96.3

67.2 47.0 70.7

77.8 27.4 1.2

5.5 25.8 73.4

15.0 12.0 11.2

1.7 34.8 14.2

a Reaction conditions: 7 mmol, substrate, 14, 12.2 or 8.4 mmol of H2O2, 22 mL of AcOEt, 0.36 g of Al2O3, 20 atm, 100 °C, 700 rpm, 8 h. b Yield of IL, IG + IIG, or IIT.

Table 5. Catalytic Activity of Alumina in the Epoxidation of Carvone under Different Reaction Conditionsa selectivity (%)

b

H2O2

time (h)

H2O2/carvone

conversion (%)

yieldb (%)

IC

IIC

others

consumption (%)

efficiency (%)

8 8 12 12

2.5 4 2.5 4

45.2 57.3 50.6 70.5

42.0 51.5 47.2 63.4

3.9 3.3 3.9 3.8

92.9 90.0 93.2 89.9

3.2 6.7 2.9 6.3

71 59 75 69

25 23 26 24

a Reaction conditions: 7 mmol of substrate, 17.5 or 28 mmol of H2O2, 22 mL of AcOEt, 0.36 g of Al2O3, 20 atm, 100 °C, 700 rpm, 8 or 12 h. Yield of IIC.

when the concentrations of reactants are increased, which deactivates the active sites of alumina. Despite these results, it must be noted that the alumina productivity for both limonene monoepoxides increases from 2.2 to 5.4 g of monoepoxide (IL+IIL)/g of alumina. To improve the conversion and selectivity with high substrate concentration, an additional experiment was performed in which the amount of alumina was increased (Table 6). It was observed that the conversion and selectivity to monoepoxides improved only to a small extent, with a decrease in alumina productivity from 5.4 to 3.2, attributable to the high amount of water produced.

On this basis, we suggest that the best way of carrying out this reaction, leading to a high yield of monoepoxides, is to remove water as it is formed. However, the removal of water must not be complete. Others studies36,37 have shown that alumina can produce the decomposition of epoxides by opening the oxirane ring in the absence of water. To check this effect in our catalytic system, an initial experiment was performed under the optimal epoxidation conditions (Table 4), but using 1,2limonene epoxide (IL) as the substrate, in the absence of hydrogen peroxide (and therefore, without water), giving other oxygenated products by rearrangement reactions with a conversion of 33%. However, in a second experiment, in which water


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a

Table 6. Effect of Reactant Concentrations on the Epoxidation of Limonene with Alumina

selectivity (%) substrate concentration (mol · L-1)

Al2O3 (g · dm-3)

conversion (%)

yieldc (%)

Al2O3 productivityd

IL

IIL

IIIL

0.25 1 1

12.9b 12.9 25.8

86.4 67.3 74.9

67.2 40.3 47.8

2.2 5.4 3.2

77.8 59.9 63.8

5.5 8.9 7.7

15.0 4.2 5.3

H2O2 others

consumption (%)

efficiency (%)

1.7 27.0 23.2

93 79 89

53 33 34

a Reaction conditions: 7 or 28 mmol of substrate, 14 or 56 mmol of H2O2, 22 or 20 mL of AcOEt, 0.36 or 0.72 g of Al2O3, 20 atm, 100 °C, 700 rpm, 8 h. b Al2O3/substrate molar ratio ) 0.5. c Yield of IL. d Al2O3 productivity expressed as mass of monoepoxide (IL+IIL) obtained/mass of alumina used.

was added to this system (at the same concentration as for hydrogen peroxide), the monoepoxide remained stable. Thus, the presence of water is necessary to stabilize the monoepoxide formed, through the transformation of strong Lewis acid sites (sOsAl+sOs), responsible for the decomposition of epoxides, into Brønsted acid sites (AlsOH or AlsOH2+) upon the adsorption of water.17 4. Conclusions The regioselective epoxidation of terpenic diolefins can be carried out using alumina, which is inexpensive and commercially available, as the catalyst, giving a high yield and selectivity to monoepoxides. Although the activity of alumina decreases significantly when it is reused after long reaction times, the initial activity can be recovered by treating it with NaOH. If the reaction is carried out at temperatures above the boiling point of the solvent (100 °C), with the pressure increased to maintain the mixture in the liquid phase, the rate of the reaction increases to a great extent. Under these conditions, it is possible to obtain the same yield of monoepoxides as obtained at 60 °C and atmospheric pressure, but with the reaction time reduced from 72 to 8 h. A second-order kinetic model is proposed to reproduce the experimental conversion data of carvone and limonene. This model takes into account the effect of substrate concentration and catalyst weight on the reaction rate. The following conclusions have been drawn after studying the effects of temperature, pressure, stirring rate, water concentration, alumina loading, and hydrogen peroxide concentration: (i) Increasing the temperature improves the substrate conversion but decreases the selectivity to epoxides, as a result of secondary reactions that lead to the higher formation of byproducts. (ii) Pressure shows a negligible effect in the studied range (from 4 to 40 atm). (iii) The stirring rate has a great influence on the conversion in the reactor used in the present study in the range from 100 to 500 rpm. The external mass-transfer resistance is not controlling for higher stirring rates. (iv) If water is added to the reaction medium, the conversion and selectivity decrease, with larger decreases for the least reactive substrate. (v) An increase in the alumina loading results in increases in the conversion and selectivity. (vi) An increase in the hydrogen peroxide concentration leads to a significant increase in conversion, but the selectivity to monoepoxides decreases as a result of the higher formation of both diepoxide and byproducts. After studying the effect of reactant concentrations (substrate, hydrogen peroxide, and alumina) on the epoxidation of limonene, we suggest that the best way of carrying out the epoxidation with a high yield of monoepoxides is to remove water from the reaction medium as it is formed. However, the

water should not be removed completely, to increase the stability of the monoepoxides in the presence of alumina. Acknowledgment Financial support from the Ministerio de Educacioń y Ciencia of Spain (Project PPQ2002-00570) is gratefully acknowledged. Nomenclature A ) pre-exponential factor CA ) substrate concentration CA0 ) initial substrate concentration DAB ) molecular diffusion coefficient of substrate A in solvent B De ) effective diffusion coefficient EA ) activation energy k ) kinetic rate constant n ) reaction order nA ) number of moles of substrate A nA0 ) initial number of moles of substrate A r ) particle radius R ) ideal gas law constant T ) temperature V ) liquid volume W ) catalyst weight ε ) particle porosity Fp ) particle density τ ) tortuosity Φ ) Thiele modulus

Literature Cited (1) Fiege, H., Ed.; Ullmann’s Encyclopedia of Industrial Chemistry, 6th ed.; Wiley-VCH: Weinheim, Germany, 2002. (2) Anastas, P. T.; Bartlett, L. B.; Kirchhoff, M. M.; Williamson, T. C. The role of catalysis in the design, development, and implementation of green chemistry. Catal. Today 2000, 55, 11. (3) Lane, B. S.; Burgess, K. Metal-catalyzed epoxidations of alkenes with hydrogen peroxide. Chem. ReV. 2003, 103, 2457. (4) Grigoropoulou, G.; Clark, J. H.; Elings, J. A. Recent developments on the epoxidation of alkenes using hydrogen peroxide as an oxidant. Green Chem. 2003, 5, 1. (5) Arends, I.W.C.E.; Sheldon, R. A. Recent developments in selective catalytic epoxidations with H2O2. Top. Catal. 2002, 19, 133. (6) De Vos, D. E.; Sels, B. F.; Jacobs, P. A. Practical heterogeneous catalysts for epoxide production. AdV. Synth. Catal. 2003, 345, 457. (7) Cagnoli, M. V.; Casuscelli, S. G.; Alvarez, A. M.; Bengoa, J. F.; Gallegos, N. G.; Samaniego, N. M.; Crivello, M. E.; Ghione, G. E.; Pe´rez, C. F.; Herrero, E. R.; Marchetti, S. G. Clean limonene epoxidation using Ti-MCM-41 catalyst. Appl. Catal. A 2005, 287, 227. (8) Cativiera, C.; Fraile, J. M.; Garcıá, J. I.; Mayoral, J. A. A new titanium-silica catalyst for the epoxidation of alkenes. J. Mol. Catal. A: Chem. 1996, 112, 259. (9) Arnold, U.; Serpa da Cruz, R.; Mandelli, D.; Schuchardt, U. Activity, selectivity and stability of metallosilicates containing molybdenum for the epoxidation of alkenes. J. Mol. Catal. A: Chem. 2001, 165, 149. (10) Casuscelli, S. G.; Crivello, M. E.; Perez, C. F.; Ghione, G.; Herrero, E. R.; Pizzio, L. R.; Va´zquez, P. G.; Caćeres, C. V.; Blanco, M. N. Effect

4680


of reaction conditions on limonene epoxidation with H2O2 catalyzed by supported Keggin heteropolycompounds. Appl. Catal. A 2004, 274, 115. (11) Aramendıá, M. A.; Borau, V.; Jimeńez, C.; Luque, J. M.; Marinas, J. M.; Ruiz, J. R.; Urbano, F. J. Epoxidation of limonene over hydrotalcitelike compounds with hydrogen peroxide in the presence of nitriles. Appl. Catal. A 2001, 216, 257. (12) Kabalka, G. W.; Pagni, R. M. Organic reactions on alumina. Tetrahedron 1997, 53, 7999. (13) Rebek, J.; McCready, R. New epoxidation reagents derived from alumina and silicon. Tetrahedron Lett. 1979, 45, 4337. (14) Rinaldi, R.; Schuchardt, U. On the paradox of transition-metalfree alumina-catalyzed epoxidation with aqueous hydrogen peroxide. J. Catal. 2005, 236, 335. (15) Rinaldi, R.; Fujiwara, F. Y.; Schuchardt, U. Chemical and physical changes related to the deactivation of alumina used in catalytic epoxidation with hydrogen peroxide. J. Catal. 2007, 245, 454. (16) Mandelli, D.; van Vliet, M. C. A.; Sheldon, R. A.; Schuchardt, U. Alumina-catalyzed alkene epoxidation with hydrogen peroxide. Appl. Catal. A 2001, 219, 209. (17) Rinaldi, R.; Schuchardt, U. Factors responsible for the activity of alumina surfaces in the catalytic epoxidation of cis-cyclooctene with aqueous H2O2. J. Catal. 2004, 227, 109. (18) Choudhary, V. R.; Patil, N. S.; Chaudhari, N. K.; Bhargava, S. K. Epoxidation of styrene by anhydrous hydrogen peroxide over boehmite and alumina catalyst with continuous removal of the reaction water. J. Mol. Catal. A: Chem. 2004, 227, 217. (19) Van Vliet, M. C. A.; Mandelli, D.; Arends, I.W.C.E.; Schuchardt, U.; Sheldon, R. A. Alumina: A cheap, active and selective catalyst for epoxidations with (aqueous) hydrogen peroxide. Green Chem. 2001, 3, 243. (20) Sepulveda, J.; Teixeira, S.; Schuchardt, U. Alumina-catalyzed epoxidation of unsaturated fatty esters with hydrogen peroxide. Appl. Catal. A 2007, 318, 213. (21) Van Vliet, M. C. A.; Arends, I. W. C. E.; Sheldon, R. A. Perfluoroheptadecan-9-one: A selective and reusable catalyst for epoxidations with hydrogen peroxide. Chem. Commun. 1999, 263. (22) Ten Brink, G. J.; Fernandez, B. C. M.; van Vliet, M. C. A.; Arends, I. W. C. E.; Sheldon, R. A. Selenium catalysed oxidations with aqueous hydrogen peroxide. Part I: Epoxidation reactions in homogeneous solution. J. Chem. Soc., Perkin Trans. I 2001, 224. (23) Majetich, G.; Hicks, R.; Sun, G.; McGill, P. Carbodiimide-promoted olefin epoxidation with aqueous hydrogen peroxide. J. Org. Chem. 1998, 63, 2564. (24) Yao, H.; Richardson, D. E. Epoxidation of alkenes with bicarbonateactivated hydrogen peroxide. J. Am. Chem. Soc. 2000, 122, 3220.

(25) Uguina, M. A.; Delgado, J. A.; Rodrı´guez, A.; Carretero, J.; Go´mezDıáz, D. Alumina as heterogeneous catalyst for the regioselectivity epoxidation of terpenic diolefins with hydrogen peroxide. J. Mol. Catal. A: Chem. 2006, 256, 208. (26) Cohen, I.; Purcell, T. Spectrophotometric determination of hydrogen peroxide with 8-quinolinol. Anal. Chem. 1967, 39, 131. (27) Morterra, C.; Magnacca, G. A case study: Surface chemistry and surface structure of catalytic aluminas, as studied by vibrational spectroscopy of adsorbed species. Catal. Today 1996, 27, 497. (28) Kasprzyk-Hordern, B. Chemistry of alumina, reactions in aqueous solution and its application in water treatment. AdV. Colloid Interface Sci. 2004, 110, 19. (29) Kno¨zinger, H.; Ratnasamy, P. Catalytic aluminas: Surface models and characterization of surface site. Catal. ReV.-Sci. Eng. 1978, 17, 31. (30) Busca, G.; Lorenzelli, V.; Sanchez Escribano, V.; Guidetti, R. FTIR study of the surface properties of the spinels NiAl2O4 and CoAl2O4 in relation to those of transitional aluminas. J. Catal. 1991, 131, 167. (31) Busca, G.; Lorenzelli, V.; Ramis, G.; Willey, R. J. Surface sites on spinel-type and corundum-type metal oxide powders. Langmuir 1993, 9, 1492. (32) Roberge, D. M.; Buhl, D.; Niederer, J. P. M.; Ho¨lderich, W. F. Catalytic aspects in the transformation of pinenes to p-cymene. Appl. Catal. A 2001, 215, 111. (33) Silva J M de, S.; Vinhado, F. S.; Mandelli, D.; Schuchardt, U.; Rinaldi, R. The chemical reactivity of some terpenes investigated by alumina catalyzed epoxidation with hydrogen peroxide and by DFT calculations. J. Mol. Catal A: Chem. 2006, 252, 186. (34) Levenspiel, O. Chemical Reaction Engineering, 3rd ed.; Wiley: New York, 1999. (35) Suzuki, M. Chemical Engineering Monographs 25: Adsorption Engineering; Kodansha-Elsevier: Tokyo, 1990. (36) Taran, M.; Delmond, B. Diterpenic skeleton transformations: Alumina catalysed rearrangements of epoxides. Tetrahedron Lett. 1982, 23, 5535. (37) French, L. G.; Charlton, T. P. Rearrangement of exo-1,4:2,3diepoxy-1,2,3,4-tetrahydronaphtalene: Formation of a novel isochromene via Grob fragmentation. Heterocycles 1993, 35, 305.

ReceiVed for reView November 18, 2008 ReVised manuscript receiVed March 2, 2009 Accepted March 10, 2009 IE801763E

Regioselective Synthesis of Monoepoxides from Terpenic Diolefins

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