Table of Contents Author Guidelines Submit a Manuscript
The Scientific World Journal
Volume 2014 (2014), Article ID 578762, 5 pages
Research Article

Facile Synthesis of Pyrazole- and Benzotriazole-Containing Selenoethers

1Department of Biotechnology and Organic Chemistry, National Research Tomsk Polytechnic University, 30 Lenin Avenue, Tomsk 634050, Russia
2Department of Chemistry, Altai State Technical University, 46 Lenin Avenue, Barnaul 656038, Russia
3Institute of Petroleum Chemistry, Siberian Branch of Russian Academy of Sciences, 3 Akademicheskii Avenue, Tomsk 634055, Russia

Received 8 September 2014; Accepted 4 November 2014; Published 20 November 2014

Academic Editor: Georgiy B. Shul’pin

Copyright © 2014 Andrei S. Potapov et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Azole-containing selenoethers, 1,5-bis(3,5-dimethylpyrazol-1-yl)-3-selena pentane and 1,3-bis(1,2,3-benzotriazol-1-yl)-2-selena propane were prepared by the reaction of corresponding tosylate or chloride with sodium selenide generated in situ from elemental selenium and sodium formaldehydesulfoxylate (rongalite).

1. Introduction

Organoselenium compounds find applications due to their biological activity and useful synthetic properties (see [1, 2] and references cited therein). Selenoethers demonstrate potent ligating ability towards transition and main-group elements [3]. On the other hand, azole-containing thioethers are also known for their rich coordination chemistry [4]. Therefore, ligands carrying both azole- and selenoether moieties are especially interesting in view of their coordination chemistry. Nevertheless, only a few reports on compounds of this type have appeared in literature, demonstrating their use as building blocks for supramolecular architecture [5] and as ligands for catalysts [69]. Hodage et al. demonstrated potential glutathione peroxidase-like activity of some pyrazole-containing selenoethers [10]. Recently, Pop et al. prepared a series of late transition metal complexes of pyrazole-derived selenoethers [11].

Dialkyl selenides (selenoethers) are usually prepared from alkyl halides and Se2− species, generated from various selenium compounds. Since selenide ions are very unstable towards oxygen, they are generated in situ using different reducing agents. Selenium in combination with aqueous NaOH [12], liquid ammonia and sodium [13], sodium in DMF [14], and sodium formaldehydesulfoxylate (rongalite) [15] were reported as sources of selenide ions. Other selenium compounds, such as selenium dioxide (reduced by trialkyl borohydrides) [16] or selenium tetrachloride [17], are less commonly used.

Herein we report improved methods for the preparation of pyrazole- and benzotriazole-containing selenoethers 1,5-bis(3,5-dimethylpyrazol-1-yl)-3-selena pentane (2) and 1,3-bis(1,2,3-benzotriazol-1-yl)-2-selena propane (4).

2. Results and Discussion

2.1. Synthesis of Selenoethers

In our preparation of azole-containing selenoethers we used elemental selenium and sodium formaldehydesulfoxylate (HOCH2SO2Na, rongalite) in aqueous NaOH [18]. The generated in situ sodium selenide was introduced into the reaction with 1-(2-tosyloxy ethyl)-3,5-dimethylpyrazole (1) or 1-chloromethyl benzotriazole (3) (Scheme 1). Due to low solubility of compound 3 in water acetonitrile was added to the reaction mixture in order to expedite the nucleophilic substitution. It should be noted that we found it unnecessary to carry out the reactions under nitrogen atmosphere, which is probably due to reductive atmosphere created by SO2 evolution from the excess of rongalite. Pyrazole- and benzotriazole-containing selenoethers (2 and 4) were obtained in good yields (76 and 90%) as off-white air- and moisture-stable solids even in the absence of nitrogen atmosphere. It should be noted that in our synthetic procedure selenide ions were generated using inexpensive and stable rongalite in contrast to superhydride (LiBEt3H) or NaBH4 used in previously reported methods of preparation of selenoethers 2 [10] and 4 [19]. The structures of selenoethers were confirmed by IR and NMR spectroscopy and, in case of selenoether 2, electron-impact mass-spectrometry.

Scheme 1: Synthesis of azole-selenoethers.

It is known [20] that upon reduction selenium can form diselenide ions in addition to selenides Se2−. Therefore, not only selenoethers, but also diselenides can form as a result of reactions in Scheme 1, and IR and NMR spectroscopy alone do not allow to unambiguously discern between them.

2.2. X-Ray Crystal Structure Determination

In order to establish the structures of compounds 2 and 4 we have carried out single crystal X-ray structure determinations. Single crystals of compound 4 were obtained by crystallization from acetonitrile. Compound 2 has a relatively low melting point and crystallized rapidly from various solvents, preventing the formation of single crystals. However, with copper(II) nitrate compound 2 readily gave well-formed crystals of complex suitable for X-ray structure determination. The complex [Cu(2)(NO3)2] (5) was obtained in high yield (84%); therefore selenoether 2 and not some other impurity acted as a ligand and the structure of the complex can be used for the elucidation of compound 2 structure.

Complex 5 crystallizes in a monoclinic crystal system; crystallographic parameters and details of the diffraction experiment are given in Table 1. Molecular structure of the complex is shown in Figure 1, and selected bond lengths and angles are listed in Table 2. From the structure of complex 5 it is evident that compound 2 is indeed a selenoether and not a diselenide. The lengths of C–C and C–N bonds in pyrazole rings are within the usual range [21]. The lengths of Se–C bonds (1.95-1.96 Å) are also common for acyclic selenoethers [22].

Table 1: Crystallographic data, details of data collection, and structure refinement parameters for compounds 4 and 5.
Table 2: Selected bond distances (Å) and angles (°) for compounds 4 and 5.
Figure 1: Molecular structure of compound 5. Thermal ellipsoids for nonhydrogen atoms are drawn at 50% probability level. Hydrogen atoms are omitted for clarity.

Reports on the synthesis and crystal structure of benzotriazole-containing selenoether 4 have appeared in two recent papers. Lu et al. [23] used a nucleophilic substitution reaction of pure sodium selenide with chloro-derivative 2 to prepare the selenoether in 55% yield. Das et al. [19] improved the yield up to 78% by generating Na2Se in situ from selenium and sodium borohydride. Both papers report crystal structures of prepared selenoethers, which they describe as pale-yellow crystals (m.p. 140°C [19]), readily soluble in common organic solvents. Both products appear to be the same monoselenide, and the slight differences in crystal structures are probably due to unlike packing fashion of formula units in elementary cells (monoclinic crystal system).

The crystallographic parameters, bond lengths, and angles for compound 4 are given in Tables 1 and 2. The asymmetric unit of this compound is a monoselenide (Figure 2), and the elementary cell contains four such units. The molecular structure of selenoether 4 is very similar to those reported by Das et al. and Lu et al. [19, 23]. The lengths of Se–C bonds are slightly (by 0.01 Å) longer than in previously reported structures, while C–Se–C angle is slightly sharper. The major type of intermolecular interactions, that is, probably responsible for low solubility and high melting point of compound 4, is Se–Se contacts (3.7936(3) Å, Figure 3), the length of which is in the range reported previously for selenoethers [24].

Figure 2: Molecular structure of selenoether 4. Thermal ellipsoids for nonhydrogen atoms are drawn at 50% probability level. Hydrogen atoms are omitted for clarity.
Figure 3: Se–Se intermolecular contacts in the structure of 4. Some molecules in the unit cell are not shown for clarity.

3. Conclusion

In summary, two selenoethers (pyrazole- and benzotriazole-containing, 2 and 4) were prepared using elemental selenium-rongalite system for in situ selenide ion generation. The proposed method uses inexpensive reagents, and provides higher yields compared to reported procedures.

4. Experimental

Elemental analyses were carried out on a Carlo Erba analyzer. Infrared (IR) spectra of solid samples as KBr pellets were recorded on a Nicolet 5700 (4000–400 cm−1) spectrophotometer. NMR spectra were recorded on Bruker AV300 instrument operating at 300 MHz for 1H and 75 MHz for 13C. EI MS measurements were carried out using TRACE DSQ (Thermo Electron Corporation, USA) instrument.

Single crystals of compounds 4 and 5 for crystal structure determination were mounted in inert oil and transferred to the cold gas stream of the diffractometer. The structure was determined at 153 K by conventional single crystal X-ray diffraction techniques using an automated four-circle Bruker-Nonius X8 Apex diffractometer equipped with a 2D CCD detector and graphite monochromated molybdenum source ( Å). Intensity data were collected by -scanning of narrow frames (0.5°) to 6°. Absorption correction was applied empirically by the program SADABS [25]. The structure was solved by the direct method and refined using the full-matrix least-squares technique in the anisotropic approximation for nonhydrogen atoms with the program package SHELX-97 [26]. Hydrogen atoms were localized geometrically.

Tosylate 1 [27] and chloro-derivative 3 [28] were prepared according to known procedures; sodium formaldehydesulfoxylate dihydrate (rongalite) was purchased from Acros.

4.1. 1,5-Bis(3,5-dimethylpyrazol-1-yl)-3-selena Pentane (2)

A suspension of selenium (0.395 g, 5 mmol), sodium formaldehydesulfoxylate dihydrate (3.08 g, 20 mmol), and NaOH (1.10 g, 27.5 mmol) in water (5 mL) was stirred at room temperature, until the initially formed red solution turned colorless and white precipitate of Na2Se was formed (15–20 min). Tosylate 1 (2.94 g, 10 mmol) was then added in one portion, the mixture was brought to reflux and stirring was continued for 3 hours (TLC control). After that water (30 mL) was added to the reaction mixture to dissolve the precipitated product and excess of rongalite. The solution obtained was extracted with chloroform (mL); the extract was dried over anhydrous Na2SO4. After removal of solvent, slightly yellow oil was obtained, which crystallized on standing at room temperature. The product was recrystallized form hexane to give colorless crystals of selenoether 2. Yield 1.24 g (76%), mp 54–56°C (hexane). IR (ν, cm−1) 1550, 1460 (), 1298 (, Pz), 1026 (Pz breating), 776 (). 1H NMR (CDCl3): 2.16 (s, 6H, 3-CH3-Pz), 2.21 (s, 6H, 5-CH3-Pz), 2.81 (t, 4H, Hz, PzCH2CH2Se), 4.10 (t, 4H,  Hz, PzCH2CH2Se), 5.73 (s, 2H, 4-H-Pz). 13C NMR (CDCl3): 11.0 (5-CH3-Pz), 13.3 (3-CH3-Pz), 23.3 (PzCH2CH2Se), 48.9 (PzCH2CH2Se), 104.8 (4-C-Pz), 138.8 (5-C-Pz), 147.5 (3-C-Pz). EI-MS (70 eV): 326 (M+), 230 ([M-Pz]+), 203 ([M-PzCH2CH2]+), 109 ([PzCH2]+). Anal. Calc’d for C14H22N4Se (325.31): C, 51.59; H, 6.82; N, 17.22. Found: C, 51.97; H, 7.01; N, 17.70.

4.2. 1,3-Bis(1,2,3-benzotriazol-1-yl)-2-selena Propane (4)

Selenoether 4 was prepared similarly to compound 2 from 2.10 g (12.54 mmol) chloro-derivative 1, 0.50 g (6.27 mmol) of selenium, 2.31 g (15.0 mmol) of sodium formaldehydesulfoxylate dihydrate, and 1.38 g (34.5 mmol) of NaOH in 6 mL of water and 15 mL of acetonitrile. Yield 1.94 g (90%), colorless crystals, mp 182-183°C (DMF). IR (ν, cm−1) 1612, 1496, 1453 (), 754 (). 1H NMR (DMSO-d6): 6.19 (s, 4H, CH2), 7.44 (t, 2H, 5-H-Bta, Hz), 7.58 (t, 2H, 6-H-Bta, Hz), 7.97 (d, 2H, 4-H-Bta, Hz), 8.08 (d, 2H, 7-H-Bta, Hz). 13C NMR (DMSO-d6): 42.5 (CH2), 111.1 (7-C-Bta), 119.3 (4-C-Bta), 124.4 (5-C-Bta), 127.5 (6-C-Bta), 131.9 (8-C-Bta), 145.4 (9-C-Bta). Anal. Calc’d for C14H12N6Se (343.25): C, 48.99; H, 3.52. Found: C, 49.30; H, 3.83.

4.3. 1,5-Bis(3,5-dimethylpyrazol-1-yl)-3-selena Pentane-Dinitrato Copper (5)

To a solution of selenoether 2 (0.065 g, 0.2 mmol) in acetone (0.2 mL), solution of Cu (NO3)23H2O (0.048 g, 0.2 mmol) in acetone (0.2 mL) was added. After standing for 2 hours, deep-green crystals of the complex were formed, which were filtered, washed with acetone, and dried. The crystals were suitable for X-ray crystal structure determination. Yield 0.086 g (84%). IR (ν, cm−1) 1556 (), 1026 (Pz breating), 811 (). Anal. Calc’d for C14H22CuN6O6Se (512.87): C, 32.79; H, 4.32; N, 16.39. Found: C, 33.04; H, 4.50; N, 15.96.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.


The reported study was partially supported by RFBR, research Project no. 13-03-98033, and “Nauka” Project no. 4.774.2014/K.


  1. A. J. Mukherjee, S. S. Zade, H. B. Singh, and R. B. Sunoj, “Organoselenium chemistry: role of intramolecular interactions,” Chemical Reviews, vol. 110, no. 7, pp. 4357–4416, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. D. M. Freudendahl, S. A. Shahzad, and T. Wirth, “Recent advances in organoselenium chemistry,” European Journal of Organic Chemistry, vol. 2009, no. 11, pp. 1649–1664, 2009. View at Publisher · View at Google Scholar
  3. W. Levason, S. D. Orchard, and G. Reid, “Recent developments in the chemistry of selenoethers and telluroethers,” Coordination Chemistry Reviews, vol. 225, no. 1-2, pp. 159–199, 2002. View at Publisher · View at Google Scholar · View at Scopus
  4. E. Bouwman, W. L. Driessen, and J. Reedijk, “Model systems for type I copper proteins: structures of copper coordination compounds with thioether and azole-containing ligands,” Coordination Chemistry Reviews, vol. 104, no. 1, pp. 143–172, 1990. View at Publisher · View at Google Scholar · View at Scopus
  5. M. Seredyuk, M. Haukka, I. O. Fritsky et al., “Bis(3,5-dimethyl-1H-pyrazolyl)selenide—a new bidentate bent connector for preparation of 1D and 2D co-ordination polymers,” Dalton Transactions, no. 29, pp. 3183–3194, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. D. Das, P. Singh, and A. K. Singh, “Palladium and half sandwich ruthenium(II) complexes of selenated and tellurated benzotriazoles: synthesis, structural aspects and catalytic applications,” Journal of Organometallic Chemistry, vol. 695, no. 7, pp. 955–962, 2010. View at Publisher · View at Google Scholar
  7. T. Chakraborty, K. Srivastava, H. B. Singh, and R. J. Butcher, “Selenoether ligand assisted Heck catalysis,” Journal of Organometallic Chemistry, vol. 696, no. 13, pp. 2559–2564, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. K. N. Sharma, H. Joshi, V. V. Singh, P. Singh, and A. K. Singh, “Palladium(ii) complexes of pyrazolated thio/selenoethers: syntheses, structures, single source precursors of Pd4Se and PdSe nano-particles and potential for catalyzing Suzuki-Miyaura coupling,” Dalton Transactions, vol. 42, no. 11, pp. 3908–3918, 2013. View at Publisher · View at Google Scholar · View at Scopus
  9. A. Kumar, G. K. Rao, S. Kumar, and A. K. Singh, “Formation and role of palladium chalcogenide and other species in Suzuki–Miyaura and heck C–C coupling reactions catalyzed with palladium(II) complexes of organochalcogen ligands: realities and speculations,” Organometallics, vol. 33, no. 12, pp. 2921–2943, 2014. View at Publisher · View at Google Scholar
  10. A. S. Hodage, P. P. Phadnis, A. Wadawale, K. I. Priyadarsini, and V. K. Jain, “Synthesis, characterization and structures of 2-(3,5-dimethylpyrazol-1-yl) ethylseleno derivatives and their probable glutathione peroxidase (GPx) like activity,” Organic and Biomolecular Chemistry, vol. 9, no. 8, pp. 2992–2998, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Pop, D. Rosca, R. Mitea, and A. Silvestru, “New diorganoselenium(II) compounds and their behavior toward late transition metals,” Inorganica Chimica Acta, vol. 405, pp. 235–242, 2013. View at Publisher · View at Google Scholar · View at Scopus
  12. W. R. McWhinnie, “Organoselenium and organotellurium analogues of ethers and peroxides,” in The Chemistry of Organic Selenium and Tellurium Compounds, S. Patai and Z. Rappoport, Eds., vol. 2, pp. 495–539, John Wiley & Sons, Chichester, UK, 1987. View at Google Scholar
  13. R. Paetzold, U. Lindner, G. Bochmann, and P. Z. Reich, “Untersuchungen an Selen-Sauerstoff-Verbindungen. XLII. Dimethyl- und Diäthylselenoxid sowie ihre Oxoniumsalze Darstellung, Eigenschaften und Schwingungsspektren,” Zeitschrift für Anorganische und Allgemeine Chemie, vol. 352, pp. 295–308, 1967. View at Publisher · View at Google Scholar
  14. D. J. Sandman, J. C. Stark, L. A. Acampora, and P. Gagne, “A direct broadly applicable approach to the synthesis of aromatic molecular and supramolecular selenium and tellurium compounds,” Organometallics, vol. 2, no. 4, pp. 549–551, 1983. View at Publisher · View at Google Scholar · View at Scopus
  15. M. L. Bird and F. Challenger, “113. Potassium alkaneselenonates and other alkyl derivatives of selenium,” Journal of the Chemical Society (Resumed), pp. 570–574, 1942. View at Google Scholar
  16. E. Tsuchida and K. Honda, “Polarographic studies on redox reactivity of polymer–hemin complex in a hydrophobic microenvironment,” Chemistry Letters, vol. 4, no. 2, pp. 119–122, 1975. View at Google Scholar
  17. H. M. Leicester, “The reactions between mercury diaryls and selenium tetrabromide,” Journal of the American Chemical Society, vol. 60, no. 3, pp. 619–620, 1938. View at Publisher · View at Google Scholar · View at Scopus
  18. G. Sommen, A. Comel, and G. Kirsch, “Substituted selenophenes starting from ketene dithioacetals and sodium selenide,” Synlett, no. 6, pp. 855–857, 2003. View at Google Scholar · View at Scopus
  19. D. Das, M. Singh, and A. K. Singh, “Reactions of μ-dichlorobis(η3-allyl)palladium(II) with bis(1-H-benzo-triazolyl-methyl) selenide: Formation of unexpected polymeric structure with dormant Se donor site. Applications of the polymeric Pd-complexes in Heck coupling,” Inorganic Chemistry Communications, vol. 12, pp. 1120–1123, 2009. View at Publisher · View at Google Scholar
  20. W. Levason and G. Reid, “Recent developments in the chemistry of thio-, seleno- and telluro-ethers,” in Handbook of Chalcogen Chemistry: New Perspectives in Sulfur, Selenium and Tellurium, F. A. Devillanova, Ed., pp. 81–106, The Royal Society of Chemistry, Cambridge, UK, 2007. View at Google Scholar
  21. A. R. Katritzky, C. A. Ramsden, J. A. Joule, and V. V. Zhdankin, Handbook of Heterocyclic Chemistry, Elsevier, Amsterdam, The Netherlands, 2010.
  22. I. Hargittai and B. Rozsondai, “Structural chemistry of organic compounds containing selenium or tellurium,” in The Chemistry of Organic Selenium and Tellurium Compounds, S. Patai and Z. Rappoport, Eds., vol. 1, pp. 63–155, John Wiley & Sons, Chichester, UK, 1986. View at Google Scholar
  23. Y. Lu, Y. Tang, H. Gao, Z. Zhang, and H. Wang, “The synthesis, crystal structures and SOD activities of a new ligand (Lse) and Co(Lse)2(SCN)2 complex [Lse = selenium ether bis-(N-1-methyl- benzotriazole)],” Applied Organometallic Chemistry, vol. 21, no. 4, pp. 211–217, 2007. View at Publisher · View at Google Scholar
  24. M. A. Petrukhina, C. Henck, B. Li et al., “Spirocyclic sulfur and selenium ligands as molecular rigid rods in coordination of transition metal centers,” Inorganic Chemistry, vol. 44, no. 1, pp. 77–84, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. G. M. Sheldrick, SADABS Program for Empirical X-Ray Absorption Correction, Bruker-Nonius, 1990–2004.
  26. G. M. Sheldrick, “Foundations of crystallography,” Acta Crystallographica A, vol. 64, pp. 112–122, 2008. View at Publisher · View at Google Scholar
  27. W. G. Haanstra, W. L. Driessen, J. Reedijk, U. Turpeinen, and R. Hamalainen, “Unusual chelating properties of the ligand 1,8-bis(3,5-dimethyl-1-pyrazolyl)-3,6-dithiaoctane (bddo). Crystal structures of Ni(bddo)(NCS)2, Zn(bddo)(NCS)2 and Cd2(bddo)(NCS)4,” Journal of the Chemical Society, Dalton Transactions, no. 11, pp. 2309–2314, 1989. View at Publisher · View at Google Scholar · View at Scopus
  28. J. H. Burckhalter, V. C. Stephens, and L. A. R. Hall, “Proof of structures derived from the hydroxy- and amino-methylation of benzotriazole,” Journal of the American Chemical Society, vol. 74, no. 15, pp. 3868–3870, 1952. View at Publisher · View at Google Scholar · View at Scopus