Nickel ferrite nanoparticles–hydrogen peroxide: a green catalyst-oxidant combination in chemoselective oxidation of thiols to disulfides and sulfides to sulfoxides

Abstract

Nickel ferrite nanoparticles–hydrogen peroxide has been demonstrated for the first time as a green and efficient catalyst-oxidant combination in the chemoselective oxidation of thiols to disulfides and sulfides to sulfoxides. This magnetically separable catalyst was found to be reusable for five consecutive runs without appreciable change in the activity, as well as composition of the catalyst. The mechanism for the oxidation of thiols and sulfides has also been proposed.

---

1. Introduction

A method for developing operationally simple and environmentally benign protocols for the synthesis of intermediates useful in chemistry, as well as in biology is a fascinating area for research. Particularly, disulfides and sulfoxides, as well as sulfones are a few such intermediates of common interest. For instance, disulfides are known to play a crucial role in many biological, as well as chemical processes, while a few disulfides find application in oil-sweetening processes, vulcanizing agents, etc.^1–5 Oxidative coupling of thiols is the most exploited pathway in disulfide synthesis, and varieties of reagents have been reported for this important transformation.^6–13 Similar to disulfides, sulfoxides are also highly sought-after owing to their importance as valuable synthons in C–C bond forming reactions, Diels–Alder reactions, as chiral auxiliaries and for their applications in medicinal chemistry.^14–16 A considerable number of methods have been previously reported for the controlled oxidation of sulfides to sulfoxides using H₂O₂ in combination with human hemoglobin, TMSCl, ZnBr₂, ZrCl₄, etc.^17–20 Quite recently, hydrogen peroxide in combination with WO₃ nanoparticles supported on MCM-48, TiO₂ nanoparticles and magnetic nanoparticle-immobilized N-propylsulfamic acid have also been reported for the oxidation of sulfides to sulfoxides.^21–23 Although most of these methods are efficient, in view of chemical as well as biological significance of disulfides and sulfoxides, the development of an eco-benign protocol for their synthesis is highly desirable.

In recent years, magnetic nanoparticles (MNPs), owing to their easy separation by application of an external magnetic field, have emerged as a useful class of heterogeneous catalysts.^24,25 In particular, iron oxide-based nanoparticles such as magnetite (Fe₃O₄) and maghemite (γ-Fe₂O₃) have been previously explored as catalysts, as well as catalyst support in a few organic transformations.^26,27 Among other oxides, spinel ferrites (MFe₂O₄; M = Ni, Zn, Mn or Co) have received a great deal of attention due to their applications as catalyst support, in magnetic drug delivery, magnetic high-density storage, etc.^28–31 Among spinel ferrites, nickel ferrite (NiFe₂O₄) with an inverse spinel structure is an important soft magnetic material with remarkable thermal stability, large magnetic anisotropy and moderate saturation magnetization. A literature survey revealed that very little attention has been paid toward its catalytic potential in organic transformations. With these observations in mind and our continued interest in the development of eco-benign synthetic methodologies,³² we planned to explore the catalytic potential of nickel ferrite-nanoparticles in a few oxidative transformations, beginning with the studies on the oxidation of thiols, as well as sulfides using hydrogen peroxide as a green and commercially available oxidant (Scheme 1).

Scheme 1 Nickel ferrite catalyzed oxidation of (a) thiols to disulfides and (b) sulfides to sulfoxides.

Our plan on the use of spinel ferrites in the oxidation of thiols as well as sulfides is based upon the concept that the catalytic properties of AB₂O₄-type spinel ferrites strongly depend on the nature of A and B ions, their charge, as well as their distribution among the octahedral Oh and tetrahedral Td sites.³³ Reithwisch and Dumesic, during their studies on a number of spinel structures have shown that in inverse and mixed spinel structures, there exists a rapid electron exchange between M²⁺ and M³⁺ ions.³⁴ Simultaneously, it is also well known that Fe²⁺ ions during oxidation with H₂O₂ to Fe³⁺ ions, generate HO radical and OH⁻ ion.^35,36 Based on these facts, we summarised that the nickel ferrite nanoparticles–hydrogen peroxide combination would serve as a useful catalyst-oxidant combination in the oxidation of thiols, as well as sulfides. It was postulated that nickel ferrite on reaction with hydrogen peroxide would generate OH radical, which would subsequently react with thiol to furnish thiol radicals, and dimerization of thiol radicals would furnish disulfide (Scheme 2A). In addition, if this concept proves true, the planned protocol can be safely extended towards oxidation of sulfides to sulfoxides (Scheme 2B).

Scheme 2 Plausible mechanism for oxidation of (A) thiols and (B) sulfides.

2. Results and discussion

Initially, nickel ferrite (NiFe₂O₄) nanoparticles were synthesized employing controlled co-precipitation method. In a typical procedure, an aqueous 4 M solution of sodium hydroxide was added dropwise to a well-stirred solution of the stoichiometric amount of NiCl₂·6H₂O and FeCl₃·7H₂O in water. The resultant precipitate was filtered and washed several times with de-ionized water. It was dried under vacuum at 60 °C for 6 h and resultant nickel ferrite particles were sintered between 800–1000 °C for 2 h. The prepared catalyst was characterized by various spectral methods.

The powder XRD pattern for nickel ferrite is shown in Fig. 1a. The peaks in the XRD pattern were indexed in light of the natural spinel structure of MgAl₂O₄. According to the spinel structure, the planes that diffract X-rays are (220), (311), (400), (422), (511) and (440). All of the detectable peaks are indexed as NiFe₂O₄ with an inverse spinel structure and are in good agreement with the standard data (44-1485 IC DD; JCPDS).^37a The absence of extra lines in the present pattern confirms the single-phase formation of nickel ferrite. To corroborate the formation of NiFe₂O₄ as single phase, using the structural data reported by Kremenovic et al. for the cubic phase,^37d theoretical XRD patterns of NiFe₂O₄ were simulated (Fig. 1c) and were compared with the experimentally observed XRD pattern of the NiFe₂O₄ nanoparticles prepared in this study. It reveals that the simulated XRD pattern of the NiFe₂O₄ is in good agreement with the powder XRD patterns of the NiFe₂O₄ collected before and after the catalytic applications (Fig. 1a and b). The lattice parameter calculated using the XRD data was found to be 8.325 Å and was in good agreement with the value reported for the uncoated ferrite.^37b,c The crystallite size of the sample was calculated from the corrected FWHM value of (311) reflection using Scherrer's equation and was found to be ∼20 nm. The SEM image of the catalyst (Fig. 2) indicates the presence of nickel ferrite nanoparticles in aggregated form. Thus, no assertion could be made about the exact morphology of the particles. Hence, the catalyst was further analysed using TEM analysis. The TEM image (Fig. 3) shows cubic morphology of the nanoparticles of size ranging between 14 and 20 nm. The particle size estimated from the TEM image is in good agreement with that predicted using XRD data. Fig. 4 shows the hysteresis loop of the sample. A very narrow hysteresis cycle with a saturation magnetization value of 41.10 emu g⁻¹ indicates the ferrimagnetic behavior of the catalyst, which allows easy separation of the catalyst using an external magnet for possible reuse.

Fig. 1 XRD pattern of NiFe₂O₄–MNPs: (a) before use; (b) after use; (c) simulated XRD.

Fig. 2 SEM images of NiFe₂O₄–MNPs: (a) before use; (b) after use.

Fig. 3 TEM image for NiFe₂O₄ nanoparticles.

Fig. 4 Hysteresis loop for NiFe₂O₄–MNPs.

After adequate characterization of the catalyst, we initially planned to explore the catalytic potential of nickel ferrite in the oxidation of thiols. To begin with, 4-bromothiophenol 1a was selected as a model substrate, nickel ferrite nanoparticles as a catalyst and H₂O₂ as an oxidant (Scheme 1a). A set of reactions were carried out employing different catalysts, as well as an oxidant concentration in different solvents. The results summarized in Table 1 reveal that complete oxidation of 1a to corresponding disulfide 2a takes place in extremely short time with the use of 15 mol% of the catalyst, 2.5 equivalent of 30% H₂O₂ and acetonitrile as the solvent (entry 8, Table 1). On the other hand, in absence of the catalyst or oxidant, the reaction does not proceed to completion (entry 15 &16 Table 1). Under the established reaction conditions, the oxidation of 1a was also carried out using simple ferrite (Fe₃O₄), as well as copper ferrite as catalysts (entries 13 and 14, Table 1). Both these catalysts were found to be effective; however, the oxidation was quite slow and considerably less amount of disulfide 2a was obtained.

Table 1 Optimization of reaction conditions for oxidative coupling of 4-bromothiophenol, 1a

No.	Catalyst (mol%)	H2O2 (equiv.)	Solvent	Time (min)	Yield^a (%)
a Reaction conditions: 4-bromothiophenol (1 equiv.), catalyst (NiFe2O4), solvent, H2O2, RT.b Using Fe3O4 as catalyst.c Using CuFe2O4 as catalyst.
1	25	5	CH3CN	5	98
2	20	5	CH3CN	5	98
3	15	5	CH3CN	5	96
4	10	5	CH3CN	5, 15	90, 92
5	5	5	CH3CN	20	80
6	15	4	CH3CN	5	96
7	15	3	CH3CN	5	96
8	15	2.5	CH3CN	5	96
9	15	2	CH3CN	15	85
10	15	1.5	CH3CN	30	60
11	15	2.5	THF	30	50
12	15	2.5	CH2Cl2	5	90
13	20^b	2.5	CH3CN	40	80
14	20^c	2.5	CH3CN	40	85
15	—	2.5	CH3CN	120	20
16	15	—	CH3CN	120	30

---

Based upon this experimental data, nickel ferrite nanoparticles were selected as the catalyst to examine the generality of the reaction conditions, as well as scope of the protocol. Accordingly, a few representative aromatic, as well as aliphatic thiols were subjected to oxidation under the optimized reaction conditions. In each case, corresponding disulfide, 2_b–j, were obtained in excellent yield, with high purity in a very short time (Table 2).

Table 2 Nickel ferrite catalyzed oxidation of thiols to disulfides^a

Entry	Product	Time (min)	Yield^b (%)
a Reaction conditions: thiol (2 mmol), catalyst (15 mol%, 0.07 g), acetonitrile (5 mL), H2O2 (2.5 equiv., 30%, 0.6 mL), RT.b Yields refer to pure isolated products.
a		5	96
b		5	94
c		5	94
d		5	92
e		5	93
f		5	88
g		7	89
h		8	95
i		10	94
j		10	92

---

Encouraged with this initial success on the oxidation of thiols to disulfides, we then turned our attention towards the oxidation of sulfides to sulfoxides (Scheme 2B). Accordingly, thioanisole, 3a, was chosen as the substrate, and it was observed that under the reaction conditions established for the oxidation of thiols, the oxidation of thioanisole proceeds smoothly to furnish corresponding sulfoxide as the only product (TLC), but it requires slightly longer time (2 h). Most interestingly, either upon the use of an excess amount of oxidant or upon stirring the reaction mixture overnight, we did not notice the formation of sulfone as an over-oxidation product (TLC, Table 3, entry a). Hence, without the modification of the reaction conditions, we planned to examine the scope of the developed protocol. Initially, thioethers bearing electron-donating as well as electron-withdrawing groups on aromatic rings were subjected to oxidation under the established reaction conditions. In each case, corresponding sulfoxide was obtained in excellent yield (Table 3, entries 4a–f). Thus, to check the functional group compatibility in this oxidative transformation, thioethers containing alcohol, nitrile, aldehyde, ketone, and ester groups, as well as an unsaturation centre were then subjected to oxidation. In all cases, corresponding sulfoxides were obtained in excellent yield (4g–o, Table 3), and no side products or over-oxidation products were observed.

Table 3 Chemoselective oxidation of sulfides to sulfoxides^a

Entry	Product	Time (h)	Yield^b (%)
a Reaction conditions: sulfide (2 mmol), catalyst (15 mol%, 0.07 g), acetonitrile (5 mL), H2O2 (2.5 equiv., 30%, 0.6 mL), RT.b Yields refer to pure isolated products.c In absence of oxidant.d Using 5.0 equiv. (1.2 mL) 30% H2O2.
a		2.0	90
		24	90
		6.0	NR^c
		2.0	92^d
b		2.0	87
c		2.5	90
d		3.5	88
e		1.5	90
f		3.5	85
g		2.0	84
h		2.5	85
i		3.0	90
j		3.0	87
k		2.0	85
l		2.5	87
m		3.5	90
n		2.0	92
o		2.5	88

---

Heterogeneously catalyzed reactions generally offer an advantage of the possibility of catalyst reuse. Hence, upon completion of the model reaction, the catalyst was separated by the application of an external magnet (Fig. 5). The recovered catalyst was washed with acetone, dried in oven at 80 °C for 3 hours and reused for the next run. It was observed that the catalyst could be recycled efficiently for five cycles without appreciable loss in its activity (Fig. 6). So as to check the stability of the catalyst during recycling, the SEM and XRD spectra of the catalyst recovered after fifth cycle were recorded (Fig. 1b and 2b). Comparison of the SEM images and XRD pattern reveals that although the morphology of the catalyst does not change appreciably (Fig. 2a and b), as evidenced from the increased peak width in the XRD pattern (Fig. 1a and b), the grain size of the particles obtained after use decreased.³⁸ Lately, the leaching behavior of the catalyst was tested. Thus, upon completion of the model reaction, the catalyst was separated and the resultant organo-aqueous phase was examined for the presence of Fe as well as Ni by performing spot tests, as well as through AAS analysis. In both the cases, the results obtained were negative. Hence, the composition of the catalyst before and after use was then confirmed from the EDAX spectra (Fig. 7). To our delight, we did not observe any appreciable change in the composition of the catalyst.

Fig. 5 Easy separation of the catalyst by application of external magnet.

Fig. 6 Recyclability of the catalyst for oxidation of sulfides.

Fig. 7 EDAX images of NiFe₂O₄–NPs: (a) before use; (b) after use.

3. Conclusion

In conclusion, we have demonstrated for the first time, the use of nickel ferrite nanoparticles–H₂O₂ as a green catalyst-oxidant combination in oxidation of thiols to disulfides and sulfides to sulfoxides at ambient temperature. This magnetically separable catalyst can be prepared by a very simple procedure using inexpensive precursors, and the catalyst can be reused for five cycles without any significant loss in its catalytic activity. Thus, the protocol serves as a useful alternative in the synthesis of disulfides and sulfoxides.

4. Experimental

All the chemicals were purchased from Aldrich or S.D. Fine Chemicals, Mumbai. ¹H and ¹³C NMR spectra were recorded using a Bruker Avance-II spectrometer. X-ray powder diffraction was performed on a PHILIPS (PW3710) X-ray diffractometer with Cu Kα₁ radiation (λ = 1.5424 A.U.). SEM micrographs were taken on a JEOL-JEM – 6360 microscope. Magnetization curves of nickel ferrite-nanoparticles were obtained using a vibrating sample magnetometer (VSM), while EDAX spectra were recorded using a Genesis XM – 2i EDX system. TEM studies were performed using Philips CM 200 with operating voltage: 20–200 kv.

General procedure for the oxidation of thiols to disulfides and sulfides to sulfoxides

To a well-stirred solution of thiol, 1 (or sulfide, 3) (2 mmol) and H₂O₂ (30%, 2.5 equiv., 0.6 mL) in acetonitrile (5 mL), nickel ferrite-nanoparticles was added (15 mol%, 0.07 g), and stirring was continued. Upon completion of oxidation (TLC), the catalyst was separated using an external magnet. The reaction mixture, was filtered under vacuum, and the resultant residue was chromatographed over a short column of silica gel. Elution with hexane–ethyl acetate (95 : 5%, v/v) furnished pure disulfide, 2 (or sulfoxide, 4) in excellent yields.

All the synthesized compounds are known. However, they were characterised by NMR spectroscopy. For original NMR spectra of sulfoxides, please see the ESI.†

References

1. S. Oae, Organic Sulfur Chemistry; Structure and mechanism, CRC, Boca Raton, FL, 1991.
2. R. J. Cremlyn, An Introduction to Organosulfur Chemistry, Wiley & Sons, New York, 1996.
3. S. Basu, S. Satapathy, M. P. Singh and A. K. Bhatnagar, Catal. Rev.: Sci. Eng., 1993, 35, 571–576.
4. S. M. S. Chauhan, A. Kumar and K. A. Srinivas, Chem. Commun., 2003, 18, 2348–2349.
5. K. Ramdas and N. Srinivasan, Synth. Commun., 1995, 25, 227–234.
6. J. Drabowicz and M. Mikolajezyk, Synthesis, 1980, 1, 32–34.
7. W. A. Pryor, D. F. Church, C. K. Govindan and G. Crank, J. Org. Chem., 1982, 47, 156–159.
8. A. McKillop and D. Koyunu, Tetrahedron Lett., 1990, 31, 5007–5011.
9. J. L. G. Ruano, A. Parra and J. Alleman, Green Chem., 2008, 10, 706–711.
10. M. Carril, R. SanMartin, E. Dominguez and I. Tellitu, Green Chem., 2007, 9, 315–317.
11. A. Dakshinamoorthy, M. Alvaro and H. Gracia, Chem. Commun., 2010, 46, 6476–6478.
12. A. Saxena kumar and A. S. Mozumdar, J. Mol. Catal. A: Chem., 2007, 269, 35–40.
13. N. Iranpoor, H. Firouzabadi and A. Pouradi, Tetrahedron, 2002, 58, 5179–5184.
14. M. C. Carreno, Chem. Rev., 1995, 95, 1717–1760.
15. N. Khiar, I. Fernandez and F. Alcudia, Tetrahedron Lett., 1993, 34, 123–126.
16. I. Fernandez and N. Khiar, Chem. Rev., 2003, 103, 3651–3705.
17. A. Kumar and Akanksha, Tetrahedron Lett., 2007, 48, 7857–7860.
18. K. Bahrami, M. M. Khodaei, B. H. Yousefi and M. S. Arabi, Tetrahedron Lett., 2010, 51, 6939–6941.
19. X.-F. Wu, Tetrahedron Lett., 2012, 53, 4328–4331.
20. K. Bahrami, Tetrahedron Lett., 2006, 47, 2009–2013.
21. D. H. Koo, M. Kim and S. Chang, Org. Lett., 2005, 7, 5015–5018.
22. R. Mohammad, G. h. Rajabzadeh, G. Rajabzadeh, S. M. Khatami, H. Eshghi and A. Shiri, J. Mol. Catal. A: Chem., 2010, 323, 59–64.
23. A. Rostamia, B. Tahmasbia, F. Abedib and Z. Shokri, J. Mol. Catal. A: Chem., 2013, 378, 200–205.
24. S. Laurent, D. Forge, M. Port, A. Roch, C. Robic and L. V. Elst, Chem. Rev., 2008, 108, 2064–2110.
25. D. Lee, J. Lee, H. Lee, S. Jin, T. Hyeon and B. M. Kim, Adv. Synth. Catal., 2006, 348, 41–47.
26. (a) H. Yoon, S. Ko and J. Jang, Chem. Commun., 2007, 14, 1468–1470; (b) N. V. Long, Y. Yang, M. Yuasa, C. M. Thi, Y. Cao, T. Nann and M. Nogami, RSC Adv., 2014, 4, 6383–6390.
27. J. Safari, Z. Zarnegar and M. Heydarian, Bull. Chem. Soc. Jpn., 2012, 85, 1332–1338.
28. B. Karimi and E. Farhangi, Chem.–Eur. J., 2011, 17, 6056–6060.
29. K. K. Senapati, S. Roy, C. Borgohain and P. Phukan, J. Mol. Catal. A: Chem., 2012, 352, 128–134.
30. M. P. Pileni, Adv. Funct. Mater., 2001, 5, 323–336.
31. Q. Song and Z. J. Zang, J. Am. Chem. Soc., 2004, 126, 6164–6168.
32. M. A. Kulkarni, K. S. Pandit, U. P. Lad, U. V. Desai, P. P. Wadgaonkar and Z. J. Zang, C. R. Chimie, 2013, 16, 869–875.
33. Structural Inorganic Chemistry, ed. A. F. Wells, Clarendon Press, Oxford, 1984.
34. D. G. Reithwisch and J. A. Dumesic, Appl. Catal., 1986, 21, 97–109.
35. Y. Ogata and Y. Sawaki, in Organic Synthesis by oxidation with metal compounds, ed. W. J. Mijs, C. R. H. I. Jonge de, Plenum Press, New York, 1996, p. 480.
36. A. M. Dumitrescu, P. M. Samoila, V. Nica, F. Doroftei, A. R. Iordan and M. N. Palamaru, Powder Technol., 2013, 243, 9–17.
37. (a) R. Sailer, G. McCarthy, ICDD Grant in Aid, 1992; (b) W. Wheicheng, L. Shuo and W. Yiyun, J. Mater. Sci. Technol., 2008, 24, 1761–1765; (c) N. Iftimie, E. Rezlescu, P. D. Popa and N. Rezlescu, J. Optoelectron. Adv. Mater., 2006, 8, 1016–1018; (d) A. Kremenovic, B. Antic, M. Vucinic-Vasic, P. Colomban, N. Bibic, V. Kahlenberg and M. Leoni, J. Appl. Crystallogr., 2010, 43, 699–709.
38. N. Mo, Y. Y. Song and C. E. Patton, J. Appl. Phys., 2005, 97, 93901.

---

Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c4ra04095c

---