Ultrasound-Accelerated Green and Selective ... - ACS Publications

Chemical Engineering Department, Institute of Chemical Technology, Matunga, Mumbai-400019, India. In the present paper we report a novel and green ...
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Ind. Eng. Chem. Res. 2006, 45, 8829-8836

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Ultrasound-Accelerated Green and Selective Oxidation of Sulfides to Sulfoxides Naresh N. Mahamuni, Parag R. Gogate, and Aniruddha B. Pandit* Chemical Engineering Department, Institute of Chemical Technology, Matunga, Mumbai-400019, India

In the present paper we report a novel and green approach for the selective synthesis of sulfoxide from sulfide using ultrasound. Use of aqueous media and easily separable and recyclable reagents makes this process green. Hydrogen peroxide is used as an oxidizing agent. Ultrasound is used to enhance the rates of reaction and selectivity of the oxidation reaction toward the desired product (sulfoxide). The effect of various parameters such as the presence and absence of ultrasound, initial concentration of the reactants, reaction temperature, molar ratio of the reactant to the oxidizing agent, mode of addition of the oxidizing agent, presence and absence of β-cyclodextrin, and amount of β-cyclodextrin has been studied. The optimum operating conditions found for the oxidation reaction on the laboratory scale were equally effective at a scaled up version of the reaction. 1. Introduction Green, sustainable chemistry involves the design of chemical processes with a view to reduce or even eliminate the use and production of hazardous materials. Recent endeavors have focused on limiting the use of organic solvents and replacing them with new, environmentally benign reaction media. The chemical industry is interested in these cost-effective, alternative solvents and processes based on the green route. Many technologies such as the use of supercritical CO2, microwave technology, ultrasound technology, electrochemistry, and the use of ionic liquids have been explored in the past to make the chemical processes green.1,2 These processes have been used either alone or in combination.3-5 The use of ultrasound for synthesis is known to enhance the rate and selectivity of the reaction by manifolds.6,7 Reactions are carried out, virtually, at room temperature and atmospheric pressure. Mild reagents are required in the presence of ultrasound as compared to the conventional processes. A phenomenon known as cavitation is held responsible for the spectacular effects observed in the presence of ultrasound.6,7 Sulfoxides are very important intermediates used in the pharmaceutical industry, foods and flavoring agents, crop protection, veterinary drugs, and the lubricant industry. They allow the synthesis of target molecules easily as they can readily undergo asymmetric transformations, addition reactions, and C-C bond formations. Recently they have been used widely in the synthesis of drugs such as omeprazole, lansoprazole, rabeprezole, etc., which are used as gastric proton pump inhibitors (PPIs). They are used in the preparation of amino acid sulfoxides, which are used for regulation of cholesterol catabolism and antibiotic activities. Sulfoxides are also used in the preparation of a potassium channel activator, aprikalim, and the anticancer drugs sulforaphane and spasomycin.8 Many efforts have been made in the past to selectively synthesize sulfoxides from sulfides. Ali et al.9-11 have investigated the selective synthesis of sulfoxides using silica gel supported catalysts in the presence of dichloromethane as the solvent. Ravikumar et al.12 have used hexafluoro-2-propanol (HFIP) as the solvent to carry out the present oxidation. Other reports suggest the use of tetranitromethane,13 tert-butyl hypochlorite,14 periodic acid,15 IBX esters,16 and choroperbenzoic * To whom correspondence should be addressed. Tel.: +91-222414-5616. Fax: +91-22-2414-5614. E-mail: [email protected].

acid12 as oxidizing agents. These combinations of reagents or solvents on oxidation produce byproducts which are not compatible with the environment. Reports in the literature also suggest the use of complex reagents of transition metals such as vanadium,17 rhenium,18 manganese,19 molybdenum,20 and titanium,21 but the procedures to form these reagents are generally very complex and time-consuming. There are some good oxidation processes including electrochemical oxidation of sulfides which use environmentally benign reagents such as hydrogen peroxide and tetrabutyl hydroperoxide as oxidizing agents and catalysts such as titanium dioxide, titanium supported on zeolite catalysts, and biocatalysts,22-26 but sulfone is also formed as one of the products along with sulfoxide in these cases, resulting in lower selectivity for sulfoxides. Our earlier work27 on selective synthesis of sulfoxide from sulfide using ultrasound had proved that sulfoxides can be effectively and selectively synthesized even at higher conversions (with respect to sulfides) using ultrasound. Methanol was used in the earlier study as a solvent. Also it was difficult to separate the catalysts used in the study from the reaction media. Since green chemistry emphasizes the use of aqueous media as solvents instead of organic media and also easily separable and reusable reagents, it was decided to carry out the oxidation of sulfides to sulfoxides in aqueous media using ultrasound. Hydrogen peroxide has been used as an oxidizing agent because of its large availability of oxygen, lower storage and transportation costs, and environmentally clean nature.28 Since hydrogen peroxide is corrosive in nature, polyurethane gloves should be used while handling the same. Also, hydrogen peroxide should be stored in cold conditions so that it does not decompose. β-Cyclodextrin (βCD) is known to increase the solubilities of organic compounds in aqueous solutions through inclusion complex formation. Breslow29 has described in detail the working mechanism of β-cyclodextrin in aqueous media. β-Cyclodextrin was used in some cases to improve the solubilities of the reactant. Methyl phenyl sulfide (MPS) was used as a model reactant as it is known that alkyl aryl sulfides are more difficult to oxidize. The reaction mixture can be easily extracted for organic compounds using ethyl acetate and separated from the aqueous phase. When the aqueous phase is filtered and cooled to 5 °C, β-cyclodextrin is obtained quantitatively and can be recycled. Thus, the process under study is a green process with minimum byproduct formation, and all of the reagents used in the process are environmentally benign. The effect of the scale of operation (a

10.1021/ie061006l CCC: $33.50 © 2006 American Chemical Society Published on Web 11/08/2006

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Figure 1. Schematic representation of the experimental setup.

few milliliters to liters) on the extent of sulfoxide formation at an optimized set of operating parameters as obtained using laboratory-scale investigations has also been reported in the present paper. The oxidation of methyl phenyl sulfide to methyl phenyl sulfoxide (MPSO) and methyl phenyl sulfone (MPSO2) using hydrogen peroxide, in general, is shown as follows: K1

MPS + H2O2 98 MPSO + H2O K2

MPSO + H2O2 98 MPSO2 + H2O 2. Experimental Section The reactions were carried out in a conical flask made up of borosil glass with a 200 mL capacity. It was equipped with a magnetic stirrer whose speed could be controlled. An ultrasonic bath (Supersonics) was used for irradiation with ultrasound. It had dimensions of 15 cm × 15 cm × 15 cm. The frequency of the ultrasound was 22 kHz, and the rated power output was 120 W. The actual power dissipation as estimated by calorimetric measurements was ∼42 W. The reactor (i.e., the conical flask) was kept centrally in the ultrasonic bath. The distance of the bottom of the conical flask from the irradiating face (bottom) of the bath was 7.5 cm. The level of water inside the bath was 1 cm above the level of the reaction mixture inside the conical flask. The transfer of energy to the reaction mixture was independent of the variation of the operating parameters such as the amount of catalyst, ratio of various reagents, etc. within the range of concentrations studied in the present work. The detailed experimental setup is shown in Figure 1. For the scaledup version of the reaction, the whole reaction mixture (3 L) was directly taken in the bath (without using the flask) for ultrasonic irradiation. 2.1. Materials. MPS was procured from Sigma-Aldrich Ltd., Mumbai, India. It was of analytical reagent grade. MPSO and MPSO2 were also of analytical grade and were procured from Acros Organics Ltd., Mumbai. HPLC-grade methanol was procured from Merck (India) Ltd., Mumbai. Ethyl acetate of GR grade and n-hexane of synthesis grade were also procured from Merck (India). Pure β-cyclodextrin was procured from S.A. Pharma-Chem Pvt. Ltd., Mumbai. H2O2 (30%, w/v) was procured from S.D. Fine-Chem Pvt. Ltd., Mumbai. All the reagents were used as received. Demineralized water was used in all the experimentation for dilution purposes when required and was obtained using the Milli-Q gradient system of Millipore.

2.2. Experimental Procedure. Initially 0.1242 g of MPS was added to 40 mL of distilled water in a 200 mL capacity conical flask. This mixture was sonicated for 40 min in the ultrasonic bath to dissolve the maximum amount of MPS in the water. This mixture was then filtered to obtain a homogeneous mixture of MPS in water. A sample (0.9 mL) was taken from this mixture and analyzed for its concentration of MPS using HPLC, which was approximately 3.105 g/L. This was the initial sample at time t ) 0 min. A definite amount of β-cyclodextrin was then added to the reaction mixture and the resulting mixture mixed properly. A predetermined amount of 30% hydrogen peroxide was then added to the reaction mixture while simultaneously applying ultrasound. Samples (0.9 mL) were taken at regular intervals of 10 min and analyzed using HPLC for the decreasing concentration of MPS. The reaction was carried out for 2 h. The temperature of the reaction mixture was kept constant by maintaining the temperature of the water inside the bath. This was done by passing ice-cold water through a coil which was placed in the bath near the wall and 3 cm from the surface of the water (without touching the wall and near the surface of the water so that it will not disturb the cavitation field generated in the reaction mixture). No temperature controller was used. The temperatures were measured manually using a thermometer, and the flow rate of the cooling water was manually adjusted. The whole reaction mixture was then transferred into a measuring cylinder, and an equal amount of ethyl acetate was added to it for extraction of MPS, MPSO, and MPSO2. The mixture was stirred vigorously using a magnetic stirrer for 12 h. A sample (200 µL) was then taken from the organic phase (top layer) and analyzed for MPSO and MPSO2 concentrations using HPTLC, whereas the MPS concentration was measured using HPLC. All the experiments were repeated twice, and the values were within (2% of the reported average values. 2.3. Analysis. The samples were analyzed for MPS using HPLC. A KNAUER HPLC instrument equipped with an ODS HYPERSIL column and a UV detector was used for this purpose. The column has dimensions of 250 mm × 4.6 mm. The size of the packing material was 5 µm. The mobile phase used for the analysis was a mixture of methanol and water (70: 30, v/v). A flow rate of 1.0 mL/min was maintained throughout the analysis. The injection volume of the samples was 20 µL. All the samples were analyzed at a wavelength of 254 nm. The samples were analyzed on an HPTLC instrument for MPSO and MPSO2. The HPTLC instrument had a DESAGA AS-30 applicator and a DESAGA CD60 densitometer. A 20 cm × 20 cm TLC aluminum sheet coated with silica gel 60 F254 (1.05554) from Merck (India) was used as the stationary phase for the separation. The mobile phase in this case was an n-heptane/ethyl acetate (70:30, v/v) mixture. 3. Results and Discussion Initially, the experiments were carried out in the presence and absence of ultrasound using only water and no oxidizing agent. This was done to verify the oxidation of MPS in the presence of water and associated cavitation. It is a well-known fact that oxidizing species are formed in water in the presence of ultrasound due to cavitation.6 No oxidation of MPS was observed in this case. This may be because whatever small amount of oxidizing species are formed, they are either recombining before they can react with the MPS or their amount is too small to cause any oxidation of MPS. Therefore, hydrogen peroxide was used in all the further experiments as an oxidizing agent. The effect of various parameters on the oxidation of MPS was studied.

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Figure 2. Effect of the presence and absence of ultrasound at a molar ratio of MPS to H2O2 of 1:1.

Figure 3. Effect of the temperature of the reaction on MPS oxidation at a molar ratio of MPS to H2O2 of 1:1.

3.1. Effect of the Presence and Absence of Ultrasound. To study the effect of ultrasound on the oxidation of MPS, the reaction mixture was placed in the ultrasonic bath and irradiated with ultrasound for a given period of time. The silent reaction (absence of ultrasound) was carried out using a magnetic stirrer. MPS (1 mM in the completely dissolved state) as well as 30% H2O2 (1 mM) was used. All the hydrogen peroxide was added initially. The reaction was carried out at room temperature (32 °C). The results are shown in Figure 2. It can be observed easily from the figure that the rate of oxidation of MPS in the presence of ultrasound was higher than in the absence of ultrasound. The conversion of MPS in the presence of ultrasound was 92.7%, whereas it was 79.6% in the absence of ultrasound in 2 h of reaction time. This can be attributed to the fact that, in the presence of ultrasound, the available hydrogen peroxide was distributed effectively and uniformly at a faster rate than in the absence of ultrasound. The turbulence created due to cavitation enhances the rate of turbulent diffusion of hydrogen peroxide on the microscale (toward the desired reactant MPS), which is in addition to the convective mixing on the macroscale due to the acoustic streaming. On the other hand, the rate of transfer in the presence of magnetic stirring (absence of ultrasound) is only due to the convective currents generated due to the stirring. The rate of convective mixing in the presence of stirring is substantially less as compared to that of the convective and turbulent mixing in the presence of ultrasound. The higher selectivity for sulfoxide as compared to that for sulfone in both the cases was due to the stoichiometric availability of the amount of hydrogen peroxide in the reaction mixture, which avoids overoxidation

of MPS. All further experiments were done in the presence of ultrasound only. 3.2. Effect of Temperature. Temperature is one of the key operating parameters in deciding the extent of completion and the rate of reaction. The effect of temperature on the oxidation of MPS in the presence of hydrogen peroxide (1 mM concentration) was studied at reaction temperatures of 15, 32, and 55 °C. The temperature of the reaction mixture was maintained at these values using a cooling coil through which chilled water was passed for maintaining a lower temperature, and hot water was passed to maintain the higher temperature. The results are shown in Figure 3. It can be seen from Figure 3 that, as the temperature of the reaction increases from 15 to 32 to 55 °C, the rate of the reaction also increases. The conversion of MPS at 15 °C was 66.9%, whereas it increased to 92.7% at 32 °C and still increased to 99.29% at 55 °C in 2 h (most of the conversion (98.1%) was achieved within 1 h of reaction at 55 °C). This is attributed to the fact that the rise in temperature increases the kinetic rate constant of a chemical reaction due to increased rates of collision among the desired molecules. We can also note from Table 1 (entries 3-5) that the selectivity toward the desired product also decreases from practically 100% at 15 and 32 °C to 94.93% at 55 °C at the end of the reaction. This can be explained by the fact that sulfide oxidation in the presence of an oxidizing agent is a stepwise reaction in which the desired product sulfoxide can be easily overoxidized to sulfone if proper control over the operating parameters is not maintained. Also, at 55 °C the intensity of cavitational collapse is greatly reduced due to the cushioning effect of the water vapor inside collapsing bubbles.

0 100 100 100 94.93 100 100 97.71 94.68 55 84.52 87.91 89.67 90.05 80 96 93 0 79.75 92.7 66.95 99.29 89.14 98.11 95.51 95.23 98.23 99.12 98.58 97.08 93.34 100 100 100 1 mM MPS + only ultrasonic bath + 40 mL of water 1 mM MPS + 1 mM H2O2 + only magnetic stirring + 40 mL of water 1 mM MPS + 1 mM 30% H2O2 + only ultrasonic bath + 40 mL of water (32 °C) 1 mM MPS + 1 mM 30% H2O2 + only ultrasonic bath + 40 mL of water + T ) 15 °C 1 mM MPS + 1 mM 30% H2O2 + only ultrasonic bath + 40 mL of water + T ) 55 °C 0.8 mM MPS + 1 mM 30% H2O2 + only ultrasonic bath + 40 mL of water (32 °C) 0.58 mM MPS + 1 mM 30% H2O2 + only ultrasonic bath + 40 mL of water (32 °C) 0.35 mM MPS + 1 mM 30% H2O2 + only ultrasonic bath + 40 mL of water (32 °C) 1 mM MPS + 2 mM 30% H2O2 + only ultrasonic bath + 40 mL of water (32 °C) 1 mM MPS + 4 mM 30% H2O2 + only ultrasonic bath + 40 mL of water (32 °C) 1 mM MPS + 4 mM 30% H2O2 + only ultrasonic bath + 40 mL of water + 10 wt % β-CD (32 °C) 1 mM MPS + 4 mM 30% H2O2 + only US BATH + 40 mL of water + 30 wt % β-CD (32 °C) 1 mM MPS + 4 mM 30% H2O2 + only US BATH + 40 mL of water + 50 wt % β-CD (32 °C) 1 mM MPS + 4 mM 30% H2O2 + only US BATH + 40 mL of water + 100 wt % β-CD (32 °C) 1.5 times excess MPS + periodic addition of 1 mM H2O2 every 10 min till 4 mM H2O2 was added + ultrasonic bath + 40 mL of water (32 °C) 1.5 times excess MPS + periodic addition of 1 mM H2O2 every 10 min till 4 mM H2O2 was added + ultrasonic bath + 40 mL of water + 100 wt % β-CD (32 °C) scaled-up reaction: MPS (15 g) + 30% H2O2 (50 mL) + 11 g of β-CD + water (3 L) + ultrasonic bath (32 °C) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

120 120 120 120 120 120 120 120 120 120 120 120 120 120 180 180 240

experiment entry

Table 1. Extent of Conversion and Yields of Products in Different Experimental Runs

0 0 0 0 5.07 0 0 2.29 5.32 45 15.48 12.09 10.33 9.95 20 4 7

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time conversion sulfoxide sulfone (min) (%) concn (%) concn (%)

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This reduces the uniform and efficient micromixing of the oxidizing agent. Thus, when the temperature is increased above an optimum temperature, the rate of overoxidation of sulfoxide to sulfone becomes significant. Hence, it was decided to carry out all further reactions at an optimized temperature of 32 °C. 3.3. Effect of the Initial Concentration of MPS. Another key factor in deciding the overall progress of the reaction is the initial concentration of MPS. The hydrogen peroxide used was kept constant at 1 mM in all these reactions. The effect of the variation in the initial concentration of MPS (three different concentrations less than 1 mM) on the extent of conversion of MPS is shown in Figure 4 and also tabulated in Table 1 (entries 3 and 6-8). It can be observed from Figure 4 and Table 1 (entries 3 and 6-8) that, as the concentration of MPS was reduced from 1 to 0.35 mM, the selectivity of sulfoxide decreased from 100% to 97.71%. This can be attributed to the fact that, as the initial concentration of MPS decreased, the amount of oxidizing agent per unit concentration of MPS available for oxidation also increased. This increased availability of 30% hydrogen peroxide led to decreased selectivity for sulfoxide due to its overoxidation to sulfone. On the other hand, no definite trend was observed in the variation of the extent of conversion though it can be seen that, at lower concentrations of MPS, higher conversions are obtained, as possibly at lower concentrations the oxidizing agent hydrogen peroxide is in stoichiometric excess. To evaluate this phenomenon in more detail, the effect of the ratio of the reactant to the oxidizing agent was investigated. 3.4. Effect of the MPS:H2O2 Molar Ratio. It is now clear that the ratio MPS:H2O2 plays a significant role in the selectivity of the desired product sulfoxide. Thus, the effect of the molar ratio on the oxidation of MPS was studied in detail by keeping the concentration of MPS constant at 1 mM and varying the amount of 30% H2O2. The molar ratio was varied from 1:1 to 1:2 and then to 1:4. The results are shown in Figure 5. It can be seen from Figure 5 and Table 1 (entries 3, 9, and 10) that, as the molar ratio MPS:H2O2 increases from 1:1 to 1:4, the conversion increases from 92.7% to 98.23%, respectively, over the same period (2 h). Thus, it is advantageous to carry out the oxidation at a 1:4 molar ratio due to the higher rate of oxidation. This can be explained by the fact that, as the amount of available hydrogen peroxide increases, the conversion levels also increase due to increased rates of oxidation. It can also be observed from Table 1 (entries 3, 9, and 10) that, as the molar ratio increases, the selectivity of sulfoxide decreases from 100% at a 1:1 molar ratio of MPS to H2O2 to 94.68% at 1:2 and further to just 55% in the case of 1:4. Thus, maximum selectivity for sulfoxide was observed at a 1:1 molar ratio of MPS to H2O2. The decrease in sulfoxide selectivity with an increase in the molar ratio MPS:H2O2 is a direct consequence of the increased amount of available hydrogen peroxide, which further oxidizes the desired sulfoxide to the undesired sulfone. The interesting point to note here is that the rate of decrease in selectivity observed in the earlier section was far lower than the rate of decrease in the selectivity of sulfoxide in this case. This may be due to the lower levels of the initial concentration of MPS used in the case discussed in section 3.3. Thus, using lower initial concentrations and maintaining a 1:1 ratio of reactant to oxidant appear to be more beneficial in terms of achieving higher selectivities for sulfoxide. 3.5. Effect of the Presence of β-Cyclodextrin. As the selectivity obtained at higher molar ratios of MPS to H2O2 was substantially lower, β-cyclodextrin was used as an additive to improve the selectivity of sulfoxide at higher conversions of

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Figure 4. Effect of the initial concentration of MPS on the progress of the reaction.

Figure 5. Effect of the molar ratio MPS:H2O2.

Figure 6. Effect of the presence of β-cyclodextrin at a molar ratio of MPS to H2O2 of 1:4.

sulfide. It has been reported in the literature that β-cyclodextrin forms inclusion complexes of molecules in aqueous media and thus helps in improving the rates and selectivity of the desired products.27,29 The effect of the presence of β-cyclodextrin was studied at a 1:4 molar ratio of MPS to H2O2 as the lowest selectivity for sulfoxide was observed at this molar ratio. Initially, the effect was studied by taking a small amount of β-cyclodextrin (10 wt % with respect to the substrate MPS). The results are shown in Figure 6. It can be observed from Figure 6 that there is only a marginal difference in the conversion of MPS in the presence and absence of β-cyclodextrin. The conversion in the absence of β-cyclodextrin was 98.23%, whereas it was 99.12% in the presence of β-cyclodextrin in 2 h of reaction time. However, the selectivity

of the desired product increased considerably in the presence of β-cyclodextrin. Quantitatively, the ratio MPSO:MPSO2 increased from 1.22 in the absence of β-cyclodextrin to 5.46 in the presence of β-cyclodextrin. This can be explained on the basis of the inclusion complex formation theory of β-cyclodextrin in aqueous media. Breslow et al.29-32 have explained the mechanism for selective chlorination of anisole. Surendra et al.33 and Krishnaveni et al.34 have also described in detail the mechanism for the observed improved selectivity for epoxides and aldehydes in the presence of β-cyclodextrin. One can easily explain the improved selectivity for sulfoxide from these studies. Phase solubility studies on β-cyclodextrin showed a 1:1 correspondence between the molecules of MPS and β-cyclodextrin. Thus, one MPS molecule is attached to one

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Figure 7. Mechanism of MPSO formation in the presence of β-cyclodextrin.

β-cyclodextrin molecule. When a hydrogen peroxide molecule comes near the MPS molecule, oxidation of MPS to MPSO occurs. The newly formed MPSO molecule moves deeper into the β-cyclodextrin cavity and is not available for further oxidation with other hydrogen peroxide molecules. As the β-cyclodextrin cavity is of hydrophobic nature, it shields MPSO from further attack from hydrogen peroxide molecules. Thus, only sulfoxide formation is achieved. The 15% formation of sulfone in the presence of β-cyclodextrin (though it was significantly less as compared to the 45% observed in the absence of β-cyclodextrin) can be explained by the fact that not all the MPS molecules are attached to β-cyclodextrin molecules as the former are soluble in water to a certain extent and only 10% β-cyclodextrin was used in this case. These freely available MPS molecules could still be overoxidized to sulfone as explained in the earlier sections. A schematic representation of the above mechanism has been depicted in Figure 7 for a better visualization of the mechanistic details. 3.6. Effect of the Amount of β-Cyclodextrin. With an aim of further improving the selectivity of the oxidation process toward sulfoxide, it was decided to study the effect of the amount of β-cyclodextrin. The amount of β-cyclodextrin was increased in the range of 10-100 wt % with respect to the substrate MPS. The results are shown in Figure 8. One can observe from Figure 8 that as the amount of β-cyclodextrin was increased there was not much change in the behavior of the system. It can be seen from Table 1 (entries 11-14) that the conversion decreased progressively from 99.12% at 10 wt % β-cyclodextrin to 98.58% at 30 wt % to 97.08% at 50 wt % and to 93.34% at 100 wt % β-cyclodextrin. There is a nominal decrease in the conversion. This decrease in the conversion levels of MPS can be explained by the fact that, as more and more β-cyclodextrin is added to the aqueous solution, the dissolved MPS in water may start coming out of the aqueous solution due to the salting out effect. However, it can be seen that, as the amount of β-cyclodextrin increased, the selectivity for sulfoxide also increased from 84.52% to 87.91% to 89.67% to 90.05% at 10, 30, 50, and 100 wt %, respectively (Table 1, entries 11-14), but the improvement of selectivity was not substantial as compared to the increase in the concentration of β-cyclodextrin. The reasons for this were already discussed in the previous section. Thus, although it is advantageous to use β-cyclodextrin, an optimum amount of catalyst, based on the priorities for selectivity or conversion, should be used. In our case, since higher selectivity was given the priority, we used 100% β-cyclodextrin in all further experiments. This is even more important in industrial-scale operations where necessarily higher concentrations of MPS are used for synthesis. It should be noted here that β-cyclodextrin can be quantitatively recycled and thus does not have any additional implications on the raw material costs.

3.7. Effect of the Mode of Addition of H2O2. Since it was not possible to further improve the selectivity of the desired product by increasing the amount of β-cyclodextrin, it was decided to change the mode of addition of hydrogen peroxide. It was known through our earlier experience27 that controlled addition of the same amount of hydrogen peroxide over longer periods improves the conversions as well as selectivity. This effect was studied in the presence of β-cyclodextrin as well as in the absence of it at a molar ratio of 1:4 of MPS to H2O2. The effect of sudden addition of hydrogen peroxide was studied at 1 mM MPS concentration, whereas a 1.5 times excess concentration of MPS was used when periodic addition of H2O2 was used. The result of using this strategy is shown in Figure 9. It can be seen clearly from Figure 9 and Table 1 (entries 10 and 16) that the amount of the desired product MPSO increased substantially (96% MPSO) when periodic addition of hydrogen peroxide was practiced instead of addition of all the hydrogen peroxide initially (only 55% MPSO). The extent of conversion of MPS also increased when hydrogen peroxide was added in stages. The amount of product formed remained constant after some time (about 30 min), indicating that the reaction does not progress further in the case where all the available hydrogen peroxide was added at the start of the reaction. On the other hand, the product formation increased continuously with time in the case of periodic addition of hydrogen peroxide. This may be because of the fact that hydrogen peroxide after some time decomposes completely and is no longer available when dumped initially as against a continuous availability in the case of periodic addition. Also, there was not much difference in the behavior of the system in the presence and absence of β-cyclodextrin on the basis of the MPS conversion. From Table 1 (entries 10, 15, and 16), one can easily see the difference in the selectivity of sulfoxide in these three cases. The selectivity was only 55% for sulfoxide when all of the 4 mM hydrogen peroxide was added initially (at the start of the reaction). It increased to 80% when a total of 4 mM hydrogen peroxide was added periodically (1 mM hydrogen peroxide was added every 10 min). It further increased to 96% when 100 wt % β-cyclodextrin was used along with periodic addition of the total 4 mM hydrogen peroxide. This proves the beneficial effects of using gradual addition of hydrogen peroxide in the presence of β-cyclodextrin and with the use of ultrasound. The reason behind the increased selectivity in the presence of gradual addition of hydrogen peroxide is that all of the added hydrogen peroxide is used efficiently for the oxidation of MPS as it is maintained in stoichiometric amounts due to controlled addition as well as uniform distribution and micromixing in the presence of ultrasound. One can also note that an excess amount of MPS was used in studying this effect. This was done to maintain the concentration of MPS at the highest level (equal to the solubility, which is ∼1 mM in 40 mL of water as determined by preliminary experiments) in the aqueous solution. The presence of an excess amount of MPS generates heterogeneity in the system as two immiscible phases are created. An emulsion of MPS in the aqueous solution is formed. This provides extra nuclei for the cavity inception in the form of phase heterogeneity in the presence of ultrasound. This increases the number of cavitation events occurring per unit time, which further helps in uniformly distributing and micromixing the oxidizing agent as well as MPS. Thus, cavitation can also be harnessed effectively by deliberately creating a small heterogeneity in the otherwise homogeneous medium. Tuziuti et al.35 have also

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Figure 8. Effect of the amount of β-cyclodextrin at a molar ratio of MPS to H2O2 of 1:4.

Figure 9. Effect of the model of addition of hydrogen peroxide at a molar ratio of MPS to H2O2 of 1:4.

tory-scale operation, on a larger scale of operation, an additional set of experiments were carried out on a 3 L scale, keeping all the ratios of the reactants and other operating parameters the same. The selectivity of sulfoxide in this case was 93%, while the sulfone concentration was only 7% at the end of 4 h of reaction (Table 1, entry 17). The extent of conversion was also above 95%. Thus, it is clear that the optimum conditions found in laboratory-scale experimentation are equally applicable in a scaled up version of the system. 4. Conclusions

Figure 10. Kinetic studies of MPS oxidation in the presence of ultrasound using excess hydrogen peroxide and β-cyclodextrin.

reported that heterogeneous cavitation increases the rates of sonochemical reactions. 3.8. Kinetics. To understand the kinetics of the reaction in the presence of ultrasound, experiments were carried out with the following operating conditions: 1 mM initial concentration of MPS, excess hydrogen peroxide (4 mM) as the oxidizing agent, and 100 wt % β-cyclodextrin. From these kinetic experiments, it was found that the oxidation of MPS is a firstorder reaction and the rate constant for this reaction is 0.0461 min-1. The results of the kinetic experiments are shown in Figure 10. 3.9. Scaleup Studies. With an aim of investigating the dependency of the optimized conditions, established in labora-

An environmentally green process has been developed for the selective oxidation of MPS using ultrasound. A detailed study of the effect of various parameters has been done. Following are the main conclusions of the study: (1) Selective synthesis of sulfoxide using ultrasound has been successfully achieved using water as the solvent instead of methanol used in the earlier work,27 making the process green. (2) The presence of ultrasound enhances the rate as well as selectivity of the oxidation reaction significantly as compared to the conventional technique of conducting the same reaction under stirring conditions. (3) Oxidation of MPS can be carried out selectively at room temperature using ultrasound. (4) Gradual addition of hydrogen peroxide in the presence of ultrasound gives better performance (higher selectivity for sulfoxide at higher conversion levels of sulfide) as compared to the case of the addition of the entire amount of H2O2 initially. (5) A molar ratio of 1:1 of MPS to H2O2 is advantageous for a maximum selectivity of sulfoxide (100%) at lower conversions of sulfide (92.7%) (Table 1, entry 3). (6) Addition of β-cyclodextrin is advantageous for

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ReceiVed for reView August 1, 2006 ReVised manuscript receiVed September 20, 2006 Accepted September 20, 2006 IE061006L