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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Phosphorus Sulfur Silicon Relat Elem. Author manuscript; available in PMC 2010 October 20.
Published in final edited form as:
Phosphorus Sulfur Silicon Relat Elem. 2009 July; 184(7): 1920–1923.
doi:  10.1080/10426500802417000
PMCID: PMC2958088
NIHMSID: NIHMS124014

OXIDATION OF THIOLS USING K2S2O8 IN IONIC LIQUID

Abstract

A green, straightforward and novel method for oxidation of thiols to the corresponding disulfides is reported using K2S2O8 in the ionic liquid 1-butyl-3-methylimidazolium bromide [(bmim)Br] at 65–70 °C. The corresponding disulfides were obtained in excellent yield and short reaction time.

Keywords: Thiols, Disulfides, Ionic liquid, Oxidation, K2S2O8

Oxidation of thiols to the corresponding disulfides under mild conditions is a useful reaction from the point of view of biological and industrial applications. [1] Since thiols can be over oxidized, extensive research has been performed to control their oxidation at disulfide stage. [2]

The oxidation coupling of thiols to disulfides is an essential reaction in the synthesis of natural products, and further oxidation to disulfide S-oxides (thiosulfinates), 1,1-dioxides (thiosulfonates), and sulfonic acids is possible. Weak S-S bonds in these compounds impart high reactivity, [3] and in natural products, these moieties and related cyclic analogues are associated with interesting biological activity. [4]

Ionic liquids (IL) have frequently been used as a green solvent in place of conventional organic solvents being [59] superior due to their extremely low vapor pressure, excellent thermal stability, reusability and ability to dissolve many organic and inorganic substrates. [10] The application of ionic liquids as solvent and catalyst has been reported for a variety of functional group transformations but their use as acid catalysts under solvent-free conditions deserves more attention.[11]

Results and Discussion

In connection with our ongoing program on developing new methods for organic functional groups transformation, [1217] we wish to report the applications of potassium persulfate, K2S2O8 in ionic liquid, 1-butyl-3-methylimidazolium [(bmim)Br] and the use of this efficient, inexpensive and mild reagent for oxidizing a variety of aliphatic and aromatic thiols.

This method is effective for coupling of aliphatic and aromatic thiols to the corresponding disulfides. It was found that only traces of further oxidation products like S-oxides (thiosulfinates), 1,1-dioxides (thiosulfonates), and sulfonic acid are formed. A series of thiols were oxidized to disulfides rapidly using this reagent. Primary alcohol, amine, carboxylic acid, ester, and methoxy functional groups were unaffected during the oxidation (Scheme 1 and Table 1).

Table 1
Oxidation of Thiols to Disulfides a, b, c

In conclusion, this is a new and green method for oxidation of thiols to the corresponding disulfides The green chemistry, straightforward work-up, mild reaction conditions, high yields of the products, and short reaction time make this an useful method for oxidation of thiols to disulfides.

Experimental

General

Yields refer to isolated pure products after column chromatography. The products were characterized by comparison of their spectral (IR, 1H NMR) and physical data with those of authentic samples [15]. All 1H NMR spectra were recorded at 300 MHz in CDCl3 relative to TMS (0.00 ppm) and IR spectra were recorded on Shimadzu 435 IR spectrometer All reactions were carried out at room temperature in a hood with strong ventilation.

Procedure for Oxidation of Thiols to the Corresponding Disulfide. Typical Procedure

A mixture of thiophenol (10 mmol, 1.1 g), K2S2O8 (2.7 g, 10 mmol), [bmim]Br (2.7 g, 10 mmol), was ground for 1 min with a mortar and pestle. The mixture was transferred to a round bottomed flask and kept at 65–70 °C for the time specified in Table 1. The progress of the reaction was followed by TLC/GC. After the reaction was completed (Table), 20 ml of diethyl ether was added and the reaction mixture filtered through a sintered glass funnel, the filtrate transferred to a separatory funnel and washed with NaHCO3 (5%). The organic layer was dried over anhydrous Na2SO4 and the solvent removed in vacuo. The residue was purified through a short column of silica gel (cyclohexane/EtOAc, 3:1) to obtain diphenyl disulfide in 94% yield, mp 59–61 °C [Lit.16 mp 58–61 °C]. 1H NMR (CDCl3, 300 MHz): δ = 7.62-7.48 (m, 4H), 7.42-7.20 (m, 6H). IR (KBr): 459, 470, 687, 734, 1435, 1474, 1572, 3050 cm−1.

Acknowledgements

We gratefully acknowledge the funding support received for this project from the Isfahan University of Technology (IUT), I.R. Iran (A. R. H.) and Grants GM 033138, MH 065503, NS 033650 (A. E. R.) from the National Institutes of Health, USA. Further financial support from Center of Excellence in Sensor Chemistry Research (IUT) is gratefully acknowledged.

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