Ind. Eng. Chem. Res. 2011, 50, 701–704
701
Ultrasound-Promoted Oxidation of Sulfides with Hydrogen Peroxide under Catalyst-Free Conditions Praveen K. Khatri, Suman L. Jain,* and Bir Sain* Chemical Sciences DiVision, Indian Institute of Petroleum, Council of Scientific and Industrial Research, Mohkampur, Dehradun-248005, India
Ultrasonication is an advanced approach toward achieving the aim of green chemical synthesis. In this Article, we have described the unique effect of the ultrasound in the oxidation of sulfides to sulfoxides with high selectivities without any catalyst by using hydrogen peroxide as oxidant in the presence of poly(ethylene glycol) dimethylether (PEGDME500) as a recyclable reaction media under ultrasonic irradiation. The developed method offers a number of advantages such as clean, cost-effective synthesis, high selectivity, shorter reaction times, recyclability of the reaction medium, and mild reaction conditions. In the absence of PEGDME500, the reaction was found to be very slow, whereas the use of acetonitrile as solvent afforded the sulfones as major products under similar reaction conditions. 1. Introduction Green or sustainable chemistry can be defined as the designing of products or processes that minimize the use and generation of hazardous substances.1,2 To implement this goal, the development of alternative approaches such as the use of supercritical CO2, microwave technology, ultrasound technology, electrochemistry, and the use of ionic liquids has been receiving considerable interest in recent decades. Ultrasonication is one of the promising alternative approaches, which offers a number of potential advantages including higher yields, enhanced reaction rates, and purity.3-6 In addition, the reactions are carried out at room temperature, atmospheric pressure, and require mild reagents as compared to the conventional processes. The main objective of the present work is to utilize the unique effect of the ultrasonic waves in promoting a reaction without using catalyst under very mild reaction conditions. Sulfoxides are highly important intermediates for the construction of various chemically and biologically active molecules such as drugs like lansoprazole, rabeprezole, etc.7,8 In particular, chiral sulfoxides are vital as they play an important role as therapeutic agents such as antiulcer (proton pump inhibitor), antibacterial, antifungal, antiatherosclerotic, anthelmintic, antihypertensive, and cardiotonic agents.7,9,10 The oxidation of sulfides is a simple and straightforward approach that has been used widely for the preparation of sulfoxides. A variety of methods based on conventional oxidants such as peracids, MnO2, MeNO2 solution in dilute HNO3/H2SO4, iodic acid, and hypervalent iodine reagents, etc., have been well documented in the literature.11-19 However, most of the methods suffer from drawbacks such as high cost, lower oxygen content, formation of copious amounts of environmentally hazardous waste, and lower selectivity. Development of green, environmentally acceptable oxidative methodologies has become a prime area of research interest in the present day chemistry. In particular, hydrogen peroxide is a desirable oxidant due to its easy availability, high oxygen content, and formation of water as ultimate byproduct. In this context, various methods using transition metals such as vanadium-,20 rhenium-,21 iron-,22-24 manganese-,25-27 and titanium28-based catalysts with hydrogen peroxide have been reported in the literature. However, most
of the existing methods have the limitations of the use of expensive catalyst, lower selectivity for sulfoxides, and the use of volatile organic solvents. The uses of microwave, ultrasound, and ionic liquids are a step forward in developing the green, sustainable chemical synthesis. In this context, scanty reports are known for the oxidation of sulfides with hydrogen peroxide. Mahamuni and co-workers29 have reported a novel and green approach for the sulfoxidation of thioanisole with hydrogen peroxide using cyclodextrin under ultrasonic irradiation. Recently, Liu et al.30 reported a simple and environmentally benign method for the sulfoxidation of sulfides with hydrogen peroxide under catalyst-free conditions. However, the longer reaction time particularly in the case of aromatic sulfides reduces the applicability of this method. Polyethylene glycols and their ether derivatives are well-known to be inexpensive, thermally stable, non toxic, recyclable, and have been widely used for many purposes in catalysis.31-36 In this Article, we wish to report an efficient, simple, and cost-effective methodology for the oxidation of sulfides to sulfoxides with hydrogen peroxide in the presence of PEGDME500 using ultrasound irradiation under catalyst-free conditions. In the present work, we have described the efficient use of ultrasonic waves in promoting the activation of hydrogen peroxide for the selective oxidation of sulfides to sulfoxides under very mild reaction conditions (Scheme 1). 2. Experimental Section 2.1. Materials and Method. All the sulfides were purchased from Aldrich and used as received. The reactions were carried out in a conical flask of 25 mL by using ultrasonic processor (Sonicator) from Hielscher Ultrasonics, Germany. All the experiments were carried out in a conical flask of 25 mL capacity. Conversion of the sulfides and selectivity for the sulfoxides/sulfones was determined by GC-MSD by using high resolution GC-MS with an EI quadrapol mass analyzer, EM detector. Scheme 1. Ultrasound-Assisted Oxidation of Sulfides
* To whom correspondence should be addressed. E-mail: suman@ iip.res.in. 10.1021/ie1013426 2011 American Chemical Society Published on Web 12/14/2010
702
Ind. Eng. Chem. Res., Vol. 50, No. 2, 2011
Table 1. Oxidation of Thioanisole in Different Solventsa entry
solvent
time (min)
1 2 3 4 5 6b 7b 8c 9 10d 11d
H2O MeOH acetone CH2Cl2 CH3CN CH3CN PEG500 PEGDME500 PEGDME500 PEGDME500
60 60 60 90 90 20 20 60 20 20 20
H2O2 (equiv)
conversion (%)
selectivity to sulfoxide (%)b
1.5 1.5 1.5 1.5 1.5 1.5 2.5 1.5 1.5 2.0 5.0
50 35 20
>80 >87 80
50 100 65 100 100 100
20 >95 88 80
a Conditions: 1 mmol of thioanisole, 1 mL of solvent at room temperature under ultrasound. b Selective formation of sulfone. c Unidentified mixture. d Selective synthesis of sulfoxide even with excess H2O2.
2.2. General Procedure for the Oxidation of Organic Sulfides Using PEGDME500 as Solvent. A mixture containing sulfide (1 mmol) and 30% aqueous H2O2 (1.5 equiv, relative to the substrate) in PEGDME500 (1 mL) was subjected to ultrasonic irradiation for the time given in Table 2 at room temperature. After completion of the reaction (as analyzed by TLC analysis), the reaction mixture was extracted by diethyl ether, and the filtrate so obtained was reused for the next run by adding fresh H2O2 and substrate. The combined organic layer was dried over anhydrous sodium sulfate and then analyzed by high resolution GC-MS using EI quadrapol mass analyzer, EM detector. The reaction times and selectivity for the sulfoxides are given in Table 2. The remaining PEG layer was reused for the subsequent runs during recycling experiments. In case of using acetonitrile as solvent, 2.5 mmol of hydrogen peroxide was used. 3. Results and Discussion Initially, the oxidation of thioanisole was carried out in various solvents and under solvent-free conditions to see the effect of solvent. The results of these experiments are summarized in Table 1. The oxidation of thioanisole (1 mmol) with hydrogen peroxide (1.5 mmol) under catalyst and solvent-free conditions by using ultrasonic irradiation at room temperature was found to be very slow, albeit afforded the corresponding sulfoxide selectively in moderate yield (Table 1, entry 1). In protic solvents such as water and methanol, the reaction was found to be very slow, whereas no reaction occurred in acetone and dichloromethane (DCM) under similar reaction conditions. In acetonitrile, the reaction was found to be faster and yielded the corresponding sulfone in place of sulfoxide under similar reaction conditions. In case of PEG500, an intricate mixture of products was obtained, which is probably due to the presence of alcoholic groups at the end of the PEG. Interestingly, in PEGDME500, the reaction proceeded very fast and afforded the selective synthesis of sulfoxide in excellent yield within a shorter reaction time. To see the effect of ultrasonic irradiation, we also carried out the oxidation of thioanisole by using aqueous hydrogen peroxide as oxidant in PEGDME500 solvent without ultrasound. The reaction was found to be very slow and gave a trace amount of the sulfoxide after a longer reaction time (3 h). This fact clearly indicated the essential role of ultrasound in accelerating the reaction rates. Also, the reaction did not occur at 65 °C under conventional heating, and original sulfide could be recovered at the end of the reaction.
On the basis of these observations, we extended the scope of the reaction for the oxidation of various aliphatic and aromatic sulfides with hydrogen peroxide both in acetonitrile and in PEGDME500 under catalyst-free conditions by using ultrasonic irradiation at room temperature. In all cases, selective formation of sulfones was obtained in acetonitrile, whereas in PEGDME500 corresponding sulfoxides were obtained selectively in high to excellent yields. We also tested the effect of the amount of the hydrogen peroxide for the oxidation of thioanisole under the described reaction conditions. In case of acetonitrile while using a 1:1 molar ratio, the reaction gave only 50% conversion with the 100% selectivity for the sulfone. However, when we used an excess amount of hydrogen peroxide (2.5 mmol), the reaction could reach the completion and provided the quantitative yield of the oxidized product. However, in case of PEGDME500, the use of 1.5 mmol of H2O2 per mmol of substrate was found to be optimum and gave the excellent yield of the corresponding sulfoxide. After completion of the reaction, the reaction mixture was checked with potassium iodide-starch test, and no hydrogen peroxide could be detected, indicating the nonproductive decomposition of some hydrogen peroxide during this course. The use of PEGDME500 makes the developed method more environmentally benign because after completion of the reaction, the product was separated by extraction with diethyl ether and the recovered solvent could efficiently be recycled several times without significant loss in catalytic activity (seven runs). Because we have used aqueous hydrogen peroxide as oxidant in the present reaction and PEGDME500 is completely miscible with water, this makes the PEGDME500 layer continuously dilute during the recycling experiment. Therefore, after four or five runs, the aqueous layer was concentrated under reduced pressure before undergoing the next recycling experiments. The results of the recycling experiments are presented in Table 3. Although the exact mechanism for the reaction is not known, the probable mechanistic pathway is shown in Scheme 2. Recently, it was reported the oxidation of sulfides with hydrogen peroxide in water and the activation of hydrogen peroxide by hydrogen bonding. In analogy, we could assume that the activation of hydrogen peroxide by PEGDME500 could be the result of hydrogen bonding between OH of hydrogen peroxide with the oxygen of PEGDME500, as shown in Scheme 2. We can also explain the higher reaction rate in PEGDME500 than water due to the strong binding capacity of PEG. Further studies for establishing the mechanism of the reaction are being carried out. To support the proposed mechanism,37 we also carried out the oxidation of thioanisole in ethylene glycol and ethanol under similar reaction conditions. In both cases, the reaction was found to be very slow, gave poor yield of the corresponding sulfoxide, and the reaction could not be reached to the completion even after longer reaction time. In summary, we have developed a truly green ultrasoundpromoted methodology for the selective oxidation of the sulfides to sulfoxides with hydrogen peroxide in PEGDME500 solvent under catalyst-free mild reaction conditions. The unique effect of ultrasound, recycling and cost effectiveness of the reaction media PEGDME500, and mild reaction conditions makes this method more attractive both from environmental and from economical points of view. We presume that the activation of hydrogen peroxide in the developed method could be possible due to the efficient mixing of the
Ind. Eng. Chem. Res., Vol. 50, No. 2, 2011
703
a
Table 2. Ultrasound-Assisted Oxidation of Different Sulfides
a Conditions: 1 mmol of substrate, 1.5 mmol of H2O2 in PEGDME500, 2.5 mmol of H2O2 in CH3CN, under ultrasound irradiation. GC-MSD. c Determined by GC-MSD.
Table 3. Results of Recycling Experimentsa
a
Conditions: As mentioned in Table 2. b Determined by GC-MSD. c Determined by GC-MSD.
b
Determined by
704
Ind. Eng. Chem. Res., Vol. 50, No. 2, 2011
Scheme 2. Probable Mechanism for Oxidation of Sulfides
substrates under ultrasonic irradiation and electrostatic attraction of hydrogen peroxide with PEGDME500. Acknowledgment We are thankful to the director, IIP, for his kind permission to publish these results. Literature Cited (1) Rothenberg, G. Catalysis: Concepts and Green Applications; WileyVCH Verlag GmbH & Co. KGaA: Weinheim, 2008. (2) Mikami, K. Green Reaction Media in Organic Synthesis; Blackwell Publishing: Ames, IA, 2005. (3) Luche, J. L. Synthetic Organic Sonochemistry; Plenum Press: New York, 1998. (4) Cognet, P.; Ghanem-Lakhal, A.; Fabre, P. L.; Wilhelm, A. M.; Delmas, H. Application of Ultrasound Technology to Electroorganic Synthesis: Reaction of Acetophenone. Chem. Eng. Sci. 2000, 55, 2571. (5) DeLima Leite, R. H.; Cognet, P.; Wilhelm, A. M.; Delmas, H. Anodic Oxidation of 2,4-dihydroxybenzoic Acid for Wastewater Treatment: Study of Ultrasound Activation. Chem. Eng. Sci. 2002, 57, 767. (6) Cravotto, G.; Cintas, P. Power Ultrasound in Organic Synthesis: Moving Cavitational Chemistry from Academia to Innovative and Large Scale Applications. Chem. Soc. ReV. 2006, 35, 180. (7) Fernandez, I.; Khiar, N. Recent Developments in Synthesis and Utilization of Chiral Sulfoxides. Chem. ReV. 2003, 105, 3651. (8) The Synthesis of Sulfoxides, Sulfones, and Cyclic Sulfides; Patai, S., Rappoport, Z., Eds.; Wiley: New York, 1994. Simpkins, N. S. In Sulfones in Organic Synthesis; Baldwin, J. E., Magnus, P. D., Eds.; Pergamon: Oxford, 1993; pp 5-99. (9) Legros, J.; Dehli, J. R.; Bolm, C. Applications of Catalytic Asymmetric Sulfide Oxidations to the Syntheses of Biologically Active Sulfoxides. AdV. Synth. Catal. 2005, 347, 19. (10) Carreno, M. C. Applications of Sulfoxides to Asymmetric Synthesis of Biologically Active Compounds. Chem. ReV. 1995, 95, 1717. (11) Drabowski, J.; Kielbasinski, P.; Mikolajczyk, M. Synthesis of Sulfoxides; John Wiley and Sons: New York, 1994. (12) Shukla, V. G.; Salgaonkar, P. D.; Akamanchi, K. G. A Mild, Chemoselective Oxidation of Sulfides to Sulfoxides Using o-Iodoxybenzoic Acid and Tetraethylammonium Bromide as Catalyst. J. Org. Chem. 2003, 68, 5422. (13) Hajipour, A. R.; Ruoho, A. E. Benzyltriphenylphosphonium Chlorochromate (BTPPCC): An Efficient and Novel Reagent for Oxidation of Sulfides to the Corresponding Sulfoxides under Non-aqueous Conditions. Sulfur Lett. 2003, 26, 83. (14) Bravo, A.; Dordi, B.; Fontana, F.; Minisci, F. Oxidation of Organic Sulfides by Br and HO Electrophilic and Free-Radical Processes. J. Org. Chem. 2001, 66, 3232. (15) Hajipour, A. R.; Mallakpour, S. E.; Adibi, H. Selective and Efficient Oxidation of Sulfides and Thiols with Benzyltriphenylphosphonium Peroxymonosulfate in Aprotic Solvent. J. Org. Chem. 2002, 67, 8666. (16) Kakarla, R.; Dulina, R. G.; Hatzenbuhler, N. T.; Hui, Y. W.; Sofia, M. J. Simple and Efficient Method for the Oxidation of Sulfides to Sulfoxides: Application to the Preparation of Glycosyl Sulfoxides. J. Org. Chem. 1996, 61, 8347. (17) Kropp, P. J.; Breton, G. W.; Fields, J. D.; Tung, J. C.; Loomis, B. R. Surface-Mediated Reactions. 8. Oxidation of Sulfides and Sulfoxides with tert-Butyl Hydroperoxide and Oxone. J. Am. Chem. Soc. 2000, 122, 4280. (18) Park, M. Y.; Jadhav, V.; Kim, Y. H. A Simple and Selective Oxidation of Sulfides to Sulfoxides Using Tetrabutylammonium Peroxydisulfate: A Rebuttal. Synth. Commun. 2004, 34, 3367.
(19) Lakouraj, M. M.; Tajbakhsh, M.; Shirini, F.; Asady Tamani, M. V. HIO3 in the Presence of Wet SiO2: A Mild and Efficient Reagent for Selective Oxidation of Sulfides to Sulfoxides under Solvent-free Condition. Synth. Commun. 2005, 36, 807. (20) Romanelli, G. P.; Bennardi, D. O.; Palermo, V.; Va’zquez, P. G.; Tundo, P. Vanadium-Substituted Keggin Type Heteropolyacid are Used for the Selective Oxidation of Sulfides to Sulfoxides and Sulfones Using Hydrogen Peroxide. Lett. Org. Chem. 2007, 4, 544. (21) Stanger, K. J.; Wiench, J. W.; Pruski, M.; Espenson, J. H.; Kraus, G. A.; Angelici, R. J. Catalytic Oxidation of a Thioether and Dibenzothiophenes Using an Oxorhenium(V) Dithiolate Complex Tethered on Silica. J. Mol. Catal. A 2006, 243, 158. (22) Bagherzadeh, M.; Amini, M. Synthesis, Characterization and Catalytic Study of a Novel Iron(III)-tridentate Schiff Base Complex in Sulfide Oxidation by UHP. Inorg. Chem. Commun. 2009, 12, 21. (23) Baciocchi, E.; Gerini, M. F.; Lapi, A. Synthesis of Sulfoxides by the Hydrogen Peroxide Induced Oxidation of Sulfides Catalyzed by Iron Tetrakis(pentafluorophenyl)porphyrin: Scope and Chemoselectivity. J. Org. Chem. 2004, 69, 3586. (24) Egami, H.; Katsuk, T. Fe (salan)-Catalyzed Asymmetric Oxidation of Sulfides with Hydrogen Peroxide in Water. J. Am. Chem. Soc. 2007, 129, 8941. (25) Marques, A.; Marin, M.; Ruasse, M. F. Hydrogen Peroxide Oxidation of Mustard-model Sulfides Catalyzed by Iron and Manganese Tetraarylporphyrines. Oxygen Transfer to Sulfides versus H2O2 Dismutation and Catalyst Breakdown. J. Org. Chem. 2001, 66, 7588. (26) Barker, J. E.; Ren, T. Sulfide Oxygenation by Tert-butyl Hydroperoxide with Mononuclear (Me3TACN) Mn Catalysts. Tetrahedron Lett. 2005, 46, 6805. (27) Xie, F.; Fu, Z. H.; Zhong, S.; Ye, Z. P.; Zhou, X. P.; Liu, F. L.; Rong, C. Y.; Mao, L. Q.; Yin, D. L. Thioanisole Oxidation with Hydrogen Peroxide Catalyzed by Hexadentate 8-Quinolinolato Manganese(III) Complexes. J. Mol. Catal. A 2009, 307, 93. (28) Iwamoto, M.; Tanaka, Y.; Hirosumi, J.; Kita, N.; Triwahyono, S. Enantioselective Oxidation of Sulfide to Sulfoxide on Ti-containing Mesoporous Silica Prepared by a Template-ion Exchange Method. Microporous Mesoporous Mater. 2001, 48, 271. (29) Mahamuni, N. N.; Gogate, P. R.; Pandit, A. B. UltrasoundAccelerated Green and Selective Oxidation of Sulfides to Sulfoxides. Ind. Eng. Chem. Res. 2006, 45, 8829. (30) Liu, F.; Fu, Z.; Liu, Y.; Lu, C.; Wu, Y.; Xie, F.; Ye, Z.; Zhou, X.; Yin, D. A Simple and Environmentally Benign Method for Sulfoxidation of Sulfides with Hydrogen Peroxide. Ind. Eng. Chem. Res. 2010, 49, 2533. (31) Jain, S. L.; Singhal, S.; Sain, B. PEG-Assisted Solvent and Catalyst Free Synthesis of 3,4-Dihydropyrimidinones under Mild Reaction Conditions. Green Chem. 2007, 9, 740. (32) Vasudevan, V. N.; Rajender, S. V. Microwave Accelerated Suzuki Cross-Coupling Reaction in Polyethylene Glycol (PEG). Green Chem. 2001, 3, 146. (33) Haimov, A.; Neumann, R. Polyethylene Glycol as a Non Ionic Liquid Solvent for Polyoxometalate Catalyzed Aerobic Oxidation. Chem. Commun. 2002, 876. (34) Chandrasekar, S.; Narsihmulu, Ch.; Shameem, S. S.; Reddy, N. R. Osmium Tetroxide in Poly(ethylene Glycol)(PEG): a Recyclable Reaction Medium for Rapid Asymmetric Dihydroxylation under Sharpless Conditions. Chem. Commun. 2003, 1716. (35) Dickerson, T. J.; Reed, N. N.; Janda, K. D. Soluble Polymers as Scaffolds for Recoverable Catalysts and Reagents. Chem. ReV. 2002, 102, 3325. (36) Kamal, A.; Reddy, D. R. Rajendar, Polyethylene Glycol (PEG) as an Efficient Recyclable Medium for the Synthesis of β-Amino Sulfides. Tetrahedron Lett. 2006, 47, 2261. (37) One of the referees suggested we check the oxidation activity in the presence of ethanol and ethylene glycol to confirm the proposed mechanism for the activation of hydrogen peroxide.
ReceiVed for reView June 23, 2010 ReVised manuscript receiVed October 15, 2010 Accepted November 27, 2010 IE1013426
