Chemoselective synthesis of diaryl disulfides via a visible light-mediated coupling of arenediazonium tetrafluoroborates and CS2

  1. Jing Leng,
  2. Shi-Meng Wang and
  3. Hua-Li Qin

School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan 430070, PR China

  1. Corresponding author email

Associate Editor: J. A. Murphy
Beilstein J. Org. Chem. 2017, 13, 903–909. doi:10.3762/bjoc.13.91
Received 11 Jan 2017, Accepted 25 Apr 2017, Published 15 May 2017

Abstract

A highly efficient and chemoselective method for the synthesis of diaryl disulfides is developed via a visible light-promoted coupling of readily accessible arenediazonium tetrafluoroborates and CS2. This practical and convenient protocol provides a direct pathway for the assembly of a series of disulfides in an environmentally friendly manner with good to excellent yields.

Keywords: arenediazonium tetrafluoroborates; carbon disulfide; chemoselectivity; diaryl disulfides; photocatalyst

Findings

The development of methods for the functionalization of peptides and proteins under mild conditions is a current frontier in the fields of chemistry, biology and drug discovery [1-4]. Most of the pharmaceutically relevant proteins contain disulfide bonds, furthermore, the disulfide ligation and its established chemoselectivity is of great advantage for proteins’ functionalization [5]. In addition, disulfides also play valuable roles as versatile building blocks for industrial applications [6-8]. Thus, the development of methodologies for the synthesis of disulfides is rather desirable and many research groups have made great contributions to the synthesis of diaryl disulfides such as the Chandrasekaran group [9] and the Wacharasindhu group [10]. Indeed, the design of sustainable and useful transformations with applications in industry is considered of high practical value. In this context, carbon disulfide, a cheap and abundant chemical, has been widely used as reactant and solvent in both industry and materials science. For example, Batanero and co-workers reported an electrochemical transformation of carbon disulfide into diaryl disulfides [11]. Sunlight as abundant and almost infinitely available energy resource has been widely used for chemical transformations in the sense of cost, safety, availability, and environmental friendliness [12-15]. Herein, we report a visible light-mediated coupling of arenediazonium tetrafluoroborates and CS2 for the chemoselective assembly of diaryl disulfides as our continuing endeavor of utilizing arenediazonium tetrafluoroborates [16] for synthetic applications (Scheme 1).

[1860-5397-13-91-i1]

Scheme 1: Chemoselective assembly of diaryl disulfides.

We conducted our initial study with benzenediazonium tetrafluoroborate (1a) and CS2 (2) as model substrates to examine the feasibility of the formation of diphenyl disulfide (3a) (Table 1). Various solvents were screened and to our delight, it was found that the reaction of 1a and 2 in DMF and DMSO gave the desired product in a moderate yield of 54% and 53%, respectively (Table 1, entries 7 and 8). Unfortunately, under the applied conditions, the chemoselectivity of the reaction was poor, affording a mixture of unexpected diphenyl sulfide (4a) and diphenyl polysulfides (5a) as byproducts. Thus, a study to optimize the reaction conditions with regard to chemoselectivity and to minimize the formation of the byproducts was conducted.

Table 1: Solvent screening for the coupling of benzenediazonium tetrafluoroborate (1a) and CS2 (2).a

[Graphic 1]
Entry Solvents Yield 3a (%)b Yield 4a (%)b Yield 5a (%)b
1 MeOH n.d. n.d. n.d.
2 THF 36 5 n.d.
3 dioxane n.d. 14 n.d.
4 acetone n.d. n.d. n.d.
5 DCM n.d. n.d. 19
6 acetonitrile n.d. n.d. n.d.
7 DMF 54 3 31
8 DMSO 53 3 27
9 hexane n.d. n.d. 24

aReaction conditions: 1a (0.1 mmol), 2 (0.2 mmol), solvent (2 mL), rt, 6 h; byields were determined by HPLC using 3a and 4a as the external standards; the yield of 5a is based on the integration of the corresponding HPLC peaks [17,18]; n.d. = not determined.

As recently surveyed, photoredox catalysts are widely employed for the generation of radicals for diverse radical reactions [19]. Further, the application of aryl radicals generated from aryldiazonium salts under visible light irradiation has also been studied [14,15] by taking advantage of visible light as abundant and environmentally friendly energy source for organic syntheses. The photochemistry of diazonium salts has been widely studied since the early 19th century, at which time, it was noticed that benzenediazonium nitrate turns red upon exposure to sunlight due to decomposition and formation of radical species [20]. Subsequently, the photodecomposition of diazonium salts by loss of nitrogen upon exposure to light has been utilized in organic synthesis for example to remove amino groups from anilines [21] or for arylation reactions [15,22].

Based on the above research results, we envisioned that a radical pathway may facilitate the formation of diaryl disulfides. Therefore the photocatalyst Ru(bpy)3(PF6)2 (bpy = 2,2’-bipyridine) [23] and a 20 W blue-light LED were chosen as catalyst and the source of visible light, respectively for our model reaction (Table 2). A variety of solvents was evaluated and eventually, it was found that the coupling of benzenediazonium tetrafluoroborate (1a) and CS2 (2) in ethanol as the solvent gave the desired product diphenyl disulfide (3a) in 77% yield accompanied by only 8% of the undesired diphenyl polysulfides (Table 2, entry 4). Switching to DMSO as the solvent for the reaction afforded exclusively the desired product 3a in excellent yield (88%, Table 2, entry 6). Next, other sulfur sources were also examined, such as S8, NaSH, Na2S, Na2S2O3, Na2S2O4 and K2S2O8, however, none of them provided the desired product in an acceptable yield (Table 2, entries 7–13).

Table 2: Screening of the solvents and sulfur sources for the visible light-mediated coupling of benzenediazonium tetrafluoroborate (1a) and CS2 (2) and other sulfur sources in the presence of Ru(bpy)3(PF6)2 as the photocatalyst.a

[Graphic 2]
Entry Solvent Sulfur source Yield 3a (%)b Yield 4a (%)b Yield 5a (%)b
1 MeOH CS2 88 <1 10
2 H2O CS2 47 5 20
3 THF CS2 87 <1 8
4 EtOH CS2 77 n.d. 8
5 acetone CS2 79 7 3
6 DMSO CS2 88 n.d. <1
7 DMSO S8 14 9 67
8 DMSO Na2S n.d. 43 11
9 DMSO Na2S2O3 n.d. n.d. n.d.
10 DMSO Na2S2O4 n.d. n.d. n.d.
11 DMSO K2S2O8 n.d. n.d. 4
12 DMSO NaSH 22 28 14
13 DMSO (NH4)2S2O8 n.d. n.d. 4

aReaction conditions: 1a (0.1 mmol), sulfur sources (0.2 mmol), Ru(bpy)3(PF6)2 (0.001 mmol), blue light (20 W), solvents (2 mL), rt, 6 h; byields were determined by HPLC using 3a and 4a as the external standards, the yield of 5a is based on the integration of the corresponding HPLC peaks [17,18]; n.d. = not determined.

In order to maximize the yields, varying amounts of CS2 (2) were also tested (Table 3) and it was found that the CS2 loading had a considerable influence on the reaction. By decreasing the loading of CS2 from 2 equiv to 0.5 equiv, the yield of the product 3a dropped to 42%, whereas increasing amounts of CS2 did not significantly increase the yield of the product. Subsequently, different photocatalysts were investigated and it turned out that the choice of catalyst also had a significant impact on our model reaction. Ru(bpy)3Cl2 catalyzed this coupling to afford the desired product 3a in a moderate yield of 65% (Table 3, entry 8). However, when the iridium-based photocatalysts Ir(ppy)3 [24], [Ir(ppy)2(bpy)]PF6 and [Ir(ppy)2(dtbbpy)]PF6 (bpy = 2,2’-bipyridine, ppy = 2-phenylpyridine, dtbbpy = 4,4’-di-tert-butyl-2,2’-bipyridine) [25,26] were used, the product yield of diphenyl disulfide (3a) was much lower compared to reactions performed in the presence of ruthenium catalysts (Table 3, entries 9–11).

Table 3: Screening of photocatalysts for the visible light-mediated coupling of benzenediazonium tetrafluoroborate (1a) and CS2 (2).a

[Graphic 3]
Entry 2 (equiv) photocatalyst solvent Yield 3a (%)b
1 0.5 Ru(bpy)3(PF6)2 DMSO 42
2 1 Ru(bpy)3(PF6)2 DMSO 47
3 1.5 Ru(bpy)3(PF6)2 DMSO 53
4 2 Ru(bpy)3(PF6)2 DMSO 88
5 2.5 Ru(bpy)3(PF6)2 DMSO 55
6 3 Ru(bpy)3(PF6)2 DMSO 57
7 Ru(bpy)3(PF6)2 CS2 n.d.
8 2 Ru(bpy)3Cl2 DMSO 65
9 2 Ir(ppy)3 DMSO 57
10 2 Ir(ppy)2(bpy)(PF6) DMSO 73
11 2 Ir(ppy)2(dtbbpy)(PF6) DMSO 8
12 2 none DMSO 53

aReaction conditions: 1a (0.1 mmol), photocatalyst (0.001 mmol), blue light (20 W), solvent (2 mL), rt, 6 h; byields were determined by HPLC using 3a as the external standard.

A plausible reaction mechanism has been proposed and is depicted in Scheme 2. We envision that the phenyl radical I was initially generated under visible light irradiation [14,15]. Subsequently, the radical I attacked the sulfur atom of carbon disulfide to provide the intermediate II which can be converted to radical intermediate III through the cleavage of the carbon–sulfur bond accompanied with the release of a carbon sulfide [11]. The active radical intermediate III can transform into three types of products through different pathways. Firstly, diaryl disulfide 3 is obtained through a dimerization of radical intermediates III, whereas the reaction of radical III with phenyl radical I is leading to byproduct 4. Finally, radical III can react with various equivalents of CS2 with release of carbon sulfide to generate aryl-polythio radicals IV and V. The combination of the latter intermediates with radical I then finally affords polysulfides 5.

[1860-5397-13-91-i2]

Scheme 2: A plausible reaction mechanism.

To demonstrate the scope of the reaction, a series of arenediazonium tetrafluoroborates was utilized in the reaction with CS2 to generate the corresponding diaryl disulfides (Table 4). Arenediazonium tetrafluoroborates 1b–p with both, electron-withdrawing and donating groups successfully underwent transformation, affording the corresponding coupling products 3b–p in good to excellent yields (42–99%). Also sterically demanding substrates gave the desired products in good yields (3d, 3f, 3g, 3i, 3m and 3n) and functional groups such as chloro, bromo, ester, methyl, nitro, and phenyl groups were also compatible with the reaction conditions.

Table 4: Reaction scope of the visible light-mediated coupling of arenediazonium tetrafluoroborates 1 with CS2 (2).

[Graphic 4]
Substrate 1a Product 3, yieldb Substrate 1a Product 3, yieldb
[Graphic 5]
1a
[Graphic 6]
3a, 80%, 50%c
[Graphic 7]
1i
[Graphic 8]
3i, 94%, 82%c
[Graphic 9]
1b
[Graphic 10]
3b, 81%, 78%c
[Graphic 11]
1j
[Graphic 12]
3j, 99%, 85%c
[Graphic 13]
1c
[Graphic 14]
3c, 85%, 72%c
[Graphic 15]
1k
[Graphic 16]
3k, 70%
[Graphic 17]
1d
[Graphic 18]
3d, 94%
[Graphic 19]
1l
[Graphic 20]
3l, 76%
[Graphic 21]
1e
[Graphic 22]
3e, 90%
[Graphic 23]
1m
[Graphic 24]
3m, 56%
[Graphic 25]
1f
[Graphic 26]
3f, 88%
[Graphic 27]
1n
[Graphic 28]
3n, 42%
[Graphic 29]
1g
[Graphic 30]
3g, 88%
[Graphic 31]
1o
[Graphic 32]
3o, 56%
[Graphic 33]
1h
[Graphic 34]
3h, 76%
[Graphic 35]
1p
[Graphic 36]
3p, 90%c, 92%c,d

aReaction conditions: 1 (0.1 mmol), CS2 (0.2 mmol), Ru(bpy)3(PF6)2 (0.001 mmol), blue light (20 W), DMSO (2 mL), rt, 6 h; bisolated yields after chromatography on silica gel; cthe reactions were carried out with the diazonium salts 1 at a 5 mmol scale; dacetone was used as the solvent.

Conclusion

In conclusion, we have developed an efficient method for the synthesis of diaryl disulfides through the coupling of arenediazonium tetrafluoroborates and CS2. This straightforward visible light-promoted process proceeds under mild reaction conditions and is applicable for the assembly of a wide range of diaryl disulfides. Further studies to clearly understand the reaction mechanism and the synthetic applications are ongoing in our laboratory.

Supporting Information

Supporting Information File 1: Experimental procedures, characterization data and copies of 1H and 13C NMR spectra for final compounds.
Format: PDF Size: 1.6 MB Download

Acknowledgements

This work was supported by the Wuhan University of Technology.

References

  1. Bode, J. W. Curr. Opin. Drug Discovery Dev. 2006, 9, 765–775.
    Return to citation in text: [1]
  2. Pratt, M. R.; Bertozzi, C. R. Chem. Soc. Rev. 2005, 34, 58–68. doi:10.1039/b400593g
    Return to citation in text: [1]
  3. Prescher, J. A.; Dube, D. H.; Bertozzi, C. R. Nature 2004, 430, 873–877. doi:10.1038/nature02791
    Return to citation in text: [1]
  4. Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004–2021. doi:10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5
    Return to citation in text: [1]
  5. Woycechowsky, K. J.; Raines, R. T. Curr. Opin. Chem. Biol. 2000, 4, 533–539. doi:10.1016/S1367-5931(00)00128-9
    Return to citation in text: [1]
  6. Oae, S. Organic Sulfur Chemistry, Structure and Mechanism; CRC Press: Boca Raton, FL, 1991.
    Return to citation in text: [1]
  7. Cremlyn, R. J. An Introduction to Organosulfur Chemistry; John Wiley and Sons: New York, 1996.
    Return to citation in text: [1]
  8. Jocelyn, D. C. Biochemistry of the Thiol Groups; Academic Press: New York, 1992.
    Return to citation in text: [1]
  9. Bhar, D.; Chandrasekaran, S. Synthesis 1994, 785–786. doi:10.1055/s-1994-25573
    Return to citation in text: [1]
  10. Tankam, T.; Poochampa, K.; Vilaivan, T.; Sukwattanasinitt, M.; Wacharasindhu, S. Tetrahedron 2016, 72, 788–793. doi:10.1016/j.tet.2015.12.036
    Return to citation in text: [1]
  11. Barba, F.; Ranz, F.; Batanero, B. Tetrahedron Lett. 2009, 50, 6798–6799. doi:10.1016/j.tetlet.2009.09.102
    Return to citation in text: [1] [2]
  12. Ravelli, D.; Fagnoni, M.; Albini, A. Chem. Soc. Rev. 2013, 42, 97–113. doi:10.1039/C2CS35250H
    Return to citation in text: [1]
  13. Lang, X.; Chen, X.; Zhao, J. Chem. Soc. Rev. 2014, 43, 473–486. doi:10.1039/C3CS60188A
    Return to citation in text: [1]
  14. Hari, D. P.; König, B. Angew. Chem., Int. Ed. 2013, 52, 4734–4743. doi:10.1002/anie.201210276
    Return to citation in text: [1] [2] [3]
  15. Hofmann, J.; Heinrich, M. R. Tetrahedron Lett. 2016, 57, 4334–4340. doi:10.1016/j.tetlet.2016.08.034
    Return to citation in text: [1] [2] [3] [4]
  16. Qin, H.-L.; Zheng, Q.; Bare, G. A. L.; Wu, P.; Sharpless, K. B. Angew. Chem., Int. Ed. 2016, 55, 14155–14158. doi:10.1002/anie.201608807
    Return to citation in text: [1]
  17. Arisawa, M.; Tanaka, K.; Yamaguchi, M. Tetrahedron Lett. 2005, 46, 4797–4800. doi:10.1016/j.tetlet.2005.05.024
    Return to citation in text: [1] [2]
  18. Zysman-Colman, E.; Harpp, D. N. J. Org. Chem. 2003, 68, 2487–2489. doi:10.1021/jo0265481
    Return to citation in text: [1] [2]
  19. Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322–5363. doi:10.1021/cr300503r
    Return to citation in text: [1]
  20. Horspool, W. M.; Lenci, F. CRC Handbook of Organic Photochemistry and Photobiology, 2nd ed.; CRC press: Boca Raton, 2003; Vol. 1 & 2.
    Return to citation in text: [1]
  21. He, L.; Qiu, G.; Gao, Y.; Wu, J. Org. Biomol. Chem. 2014, 12, 6965–6971. doi:10.1039/C4OB01286K
    Return to citation in text: [1]
  22. Xue, D.; Jia, Z.-H.; Zhao, C.-J.; Zhang, Y.-Y.; Wang, C.; Xiao, J. Chem. – Eur. J. 2014, 20, 2960–2965. doi:10.1002/chem.201304120
    Return to citation in text: [1]
  23. Dedeian, K.; Djurovich, P. I.; Garces, F. O.; Carlson, G.; Watts, R. J. Inorg. Chem. 1991, 30, 1685–1687. doi:10.1021/ic00008a003
    Return to citation in text: [1]
  24. Slinker, J. D.; Gorodetsky, A. A.; Lowry, M. S.; Wang, J.; Parker, S.; Rohl, R.; Bernhard, S.; Malliaras, G. G. J. Am. Chem. Soc. 2004, 126, 2763–2767. doi:10.1021/ja0345221
    Return to citation in text: [1]
  25. Schank, K.; Leider, R.; Lick, C.; Glock, R. Helv. Chim. Acta 2004, 87, 869–924. doi:10.1002/hlca.200490085
    Return to citation in text: [1]
  26. Carnell, A. J.; Johnstone, R. A. W.; Parsy, C. C.; Sanderson, W. R. Tetrahedron Lett. 1999, 40, 8029–8032. doi:10.1016/S0040-4039(99)01610-X
    Return to citation in text: [1]

© 2017 Leng et al.; licensee Beilstein-Institut.
This is an Open Access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (http://www.beilstein-journals.org/bjoc)

 
Back to Article List