The Scientific World Journal
Volume 2014 (2014), Article ID 578762, 5 pages
http://dx.doi.org/10.1155/2014/578762

Research Article

Facile Synthesis of Pyrazole- and Benzotriazole-Containing Selenoethers

Andrei S. Potapov,1,2 Nina P. Chernova,² Vladimir D. Ogorodnikov,³ Tatiana V. Petrenko,³ and Andrei I. Khlebnikov1,2

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.

Abstract.

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 [6–9]. 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.

Example
4
5

Chemical formula
C₁₄H₁₂N₆Se
C₁₄H₂₂CuN₆O₆Se

M (g mol⁻¹)
343.26
512.88

Temperature (K)
100(2)
100(2)

Wavelength (Å)
0.71073
0.71073

Crystal size (mm)

Crystal system
Monoclinic
Monoclinic

Space group
P 21/c
P 21/c

(Å)
11.2605(8)
16.8873(9)

(Å)
9.1443(7)
8.3578(5)

(Å)
13.6312(10)
13.9597(8)

(°)
90
90

(°)
102.2002(13)
103.2610(10)

(°)
90
90

(Å³)
1371.90(18)
1917.74(19)

4
4

(g cm⁻³)
1.662
1.776

(mm⁻¹)
2.740
3.082

688
1036

range for data
collection (°)
1.85 to 29.00
2.48 to 29.00

Index ranges

Reflections collected
15771
22301

Independent reflections
3651
5086

Completeness to (%)
99.9
99.7

Absorption correction
Semi-empirical from equivalents
Semi-empirical from equivalents

Max. and min. transmission
0.753 and 0.700
0.913 and 0.694

Data/restraints/parameters
3651/0/190
5086/0/257

Goodness-of-fit on
1.002
1.018

Final
=

=

(all data)

Largest difference in peak and hole (e Å⁻³)
0.434 and −0.433
0.590 and −0.604

Table 2: Selected bond distances (Å) and angles (°) for compounds 4 and 5.

Compound 4

Se(1)–C(1A)
1.960(2)
N(1A)–C(1A)–Se(1)
112.83(14)

Se(1)–C(1)
1.962(2)
C(1A)–Se(1)–C(1)
95.88(9)

N(1)–C(1)
1.440(3)
N(1)–C(1)–Se(1)
111.81(13)

N(1A)–C(1A)
1.441(3)

Compound 5

Se(1)–C(7)
1.955(3)
C(7)–Se(1)–C(14)
99.87(12)

Se(1)–C(14)
1.965(3)
C(7)–Se(1)–Cu(1)
101.55(8)

Se(1)–Cu(1)
2.5110(4)
C(14)–Se(1)–Cu(1)
100.47(8)

Cu(1)–N(4)
1.965(2)
N(4)–Cu(1)–N(2)
175.68(9)

Cu(1)–N(2)
1.971(2)
N(4)–Cu(1)–O(1)
88.00(8)

Cu(1)–O(1)
2.0504(19)
N(4)–Cu(1)–Se(1)
87.11(6)

Cu(1)–O(4)
2.2700(19)
N(2)–Cu(1)–Se(1)
95.72(6)

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.

Acknowledgments

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

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