2-Methyl-4,5,6,7,8,9-hexahydrocycloocta[d][1,2,3]selenadiazol]-2-ium Iodide

Abstract

The synthesis of the first 2-alkyl-1,2,3-selenadiazol-2-ium salt is reported. Extensive spectroscopic characterization including Se-NMR was performed and the results are compared with those of the known 3-ium isomer. The yellow compound crystallizes in blocks as well as in columns. The crystal structures of both types are solved by X-ray diffraction and give final proof of the molecular structure.

1. Introduction

Cycloalkeno-1,2,3-selenadiazoles are important synthons for the preparation of strained cycloalkynes [1,2,3,4,5] and polycyclic systems [6]. Some selenadiazoles possess antimicrobial or anti-tumour activity [7,8,9,10]. Besides fragmentation to alkynes or selenium heterocycles, their chemistry remains mostly unexplored. The first selenadiazolium salt has been reported in 1965 [11] and a few reports on 1,2,4-, 1,2,5- and 2,1,3-selenadiazolium salts with annulated benzene rings mostly appeared in the recent past [12,13,14,15,16]. In 2000, Meslin prepared the first 1,2,3-selenadiazolium salt by alkylation of a selenadiazole with methyl triflate [17]. A few 2-aryl-1,2,3-selenadiazolium salts were obtained in oxidative-ring-forming reactions [18,19,20,21,22]. Recently, we reported crystal structures of cycloocteno-1,2,3-selenadiazolium salts [23,24,25]. Independent from the nature of the alkylation agent, all hitherto reported alkyl-1,2,3-selenadiazoliums salts are 3-alkyl-1,2,3-selenadiazoliums salts. Herein, we report the isolation, characterization, and X-ray structures of the first 1,2,3-selenadiazolium salt with an alkyl substituent in position 2.

2. Results

2.1. Synthesis

The synthesis of 1,2,3-selenadiazoles has been developed by Lalezari [26]. Cycloocteno-1,2,3-selenadiazole was first prepared by Meier [27] and thermally fragmented to cyclooctyne. The alkylation of cycloocteno-1,2,3-selenadiazole was performed by adding 2.5 equivalents of methyl iodide (0.8 g, 5.75 mmol) to a solution of cycloocteno-1,2,3-selenadiazole (0.49 g, 2.3 mmol) in acetonitrile (5 mL). After 14 days at ambient temperature, the solvent and excess reagent were evaporated. Chromatography on silica gel using chloroform/propanol-2 (8/1) as eluent allowed the separation of the desired minor isomer (R_f = 0.73) (0.140 g, 17% yield) from the main isomer (R_f = 0.24) (0.354 g, 44% yield) (Scheme 1). Recrystallization from chloroform/ethanol (15/1) gave yellow-orange crystals with m. p. = 163–165 °C (dec).

2.2. Spectroscopic Characterization

• IR (KBr): 2918, 2844, 1675, 1452, 1435, 1316 cm⁻¹.
• ¹H-NMR (CDCl₃, 400 MHz): δ = 4.34 (s, 3H, CH₃, satellites: ¹J_C-H 147 Hz), 3.57 (‘t’, 2 H, ³J_H-H = 6 Hz, H₂C-9), 3.04 (t, 2 H, ³J_H-H = 6 Hz, H₂C-4), 1.86 (qui, 2 H, ³J_H-H = 6 Hz, H₂C-8), 1.69 (qui, 2 H, ³J_H-H = 6 Hz, H₂C-4), 1.44 (qui, 2 H, ³J_H-H = 6 Hz, H₂C-6), 1.29 (qui, 2 H, ³J_H-H = 6 Hz, H₂C-7).
• ¹³C-NMR (CDCl₃, 100 MHz): δ = 173.2 (C-9a; satellites: ¹J_C-Se: 158.4 Hz), 158.4 (C-3a; satellites: ²J_C-Se: 51 Hz), 47.3 (CH₃, satellites: ²J_C-Se: 84.3 Hz), 33.8 (C-9), 30.9 (C-8), 30.5 (C.5), 28.0 (C-4), 26.1 (C-6), 24.7 (C-7).
• ⁷⁷Se-NMR (CDCl₃, 76.3 MHz, Me₂Se): δ = 1307.5.
• ¹⁵N-NMR: (CDCl₃, 60.8 MHz): δ = 275.68, 410.26.
• Mass Spectrometry: (field desorption): 587 (5%, Se₂-pattern, M₂-I⁻), 231.2 (100%, Se-pattern, M-I⁻), 142 (CH₃I).
• UV-Vis: Solutions of the title compound in ethanol displayed three maxima in the UV-Vis region: λ = 423 nm (ε = 1388 L/mol × cm⁻¹), λ = 290 nm (ε = 25,311 L/mol × cm⁻¹), and λ = 254 nm (ε = 26,609 L/mol × cm⁻¹), significantly different from the 3-methylselenadiazolium isomer: λ = 431 nm (ε = 1820 L/mol × cm⁻¹) and l = 269 nm (e = 19,353 L/mol × cm⁻¹). Upon continued exposure to UV, the compounds decompose.

The assignment of ¹H- and ¹³C-NMR signals is based on COSY-, HMBC- and HSQC spectra. The spectra of the title compound and the known isomer [11] are very similar; a striking difference is the much higher dispersion of the proton signals in the methylene chain of the 2-methyl isomer (six signals) compared to the 3-methyl isomer (4 signals). The sequence of the carbon signals of both isomers is identical, and the position of the methyl group only has small impact on the chemical shift in the carbon signals in the heterocycle: C3a appears at δ = 158.4 in the 2-isomer and at 154.4 in the 3-isomer, only a marginal influence of the alkylation position on the shift in the carbon bound to selenium was noted, 173.2 versus 173.7, and even the ⁷⁷Se signal shifts only about Δδ = 8 ppm deep field. ¹⁵N-resonances appear at 275.68 and 410.26. Due to a contact of the latter with the protons on C-4, this signal is attributed to N-3; consequently, the former corresponds to N-2. A comparison of the title compound with the 3-isomer (270.91, N-3; 411.41, N-2) reveals a negligible impact of selenium on the ¹⁵N-resonances. The carbon, nitrogen and selenium NMR spectra of cycloocteno-1,2,3-selenadiazole had been intensively studied by Duddeck [28]. Alkylation on N-2 of the heterocycle provokes strong upfield shifts in all but one signal (Δδ = −195 for Se, Δδ = −180 for N-2, Δδ = −54 for N-3, Δδ = −3 for C-3a but Dd = +14 for C-9a). While the chemical shifts in selenium and nitrogen in 1,2,3-selenadiazoles are very sensitive towards the size and structure of annulated rings [2,28,29,30], the impact of alkylation position in their quaternary salts is close to negligible. NMR-spectra are collected in the Supplementary Materials.

2.3. Crystal Structure

Upon recrystallization from chloroform/propanol-2, the selenadiazolium salt crystallized in two different types. The column-shaped crystals of the triclinic system contain two molecules per unit cell while the eight molecules fill the unit cell of the block-shaped, orthorhombic crystals (Figure 1).

In the block-shaped crystal, the atoms of the heterocycle and the three adjacent carbon atoms are essentially coplanar; the largest deviation from planarity is on the methyl carbon with 0.091(3) Å and even the iodide ion is close to be coplanar 0.0415(3) Å. The cyclooctene ring forms a twist-boat conformation. The carbon atoms 4, 5, 8, 9 are coplanar; this plane and the heterocycle enclose an angle of 70.49(15)°. Carbon 7 lies 0.375(2) Å above and carbon 6 lies 0.561(3) Å below the beforementioned plane. Like in isomeric 3-alkylselenadiazolium salts, the anion is in the vicinity of the selenium atom, the distance is 3.091 Å and the three atoms N-2, Se, and iodide are mostly collinear, and the angle at Se is 177.32°. The distance of the iodide to selenium of the next molecule is 3.9 Å, very much closer as the other heteroatoms. The column-shaped crystal consists of a disordered arrangement of two conformers with a ratio of 85/15. In the main conformer, two planar units, the heterocycle (max. deviation 0.012 Å) and the carbons C-4,5,8,9 (max. deviation 0.044(7) Å) enclose a dihedral angle of 71.1(4)°. Contrary to the conformation in the other crystal, carbon 6 lies 0.593(10) A above and carbon 7 -0.380(9) Å below that plane. Furthermore, the N2-Se-iodide angle amounts to 71.1(4)°; the only difference to the minor conformer is the conformation on C6A/C7A. While the former lies 0.65(4) Å below the C4,5,8,9-plane, C7A is 0.40(5) Å above that plane. A comparison of the structure of the title compound and its 3-methyl isomer [11] gives significant changes in bond lengths of the N-N-Se unit. The bond lengths in the 3-isomer are Se-N: 1.808 Å and N=N 1.302 Å whereas the 2-isomer shows a much longer N-Se bond (1.872 Å) and a short N=N bond (1.286 Å).

X-ray diffraction data are deposited at the Cambridge Crystallographic Data Centre. These data can be obtained free of charge via https://www.ccdc.cam.ac.uk/. DCCDC 2,490,669 (major conformer) and DCCDC 2,490,670 (minor conformer) contain the supplementary crystallographic data for this paper.

3. Discussion

The molecular structure and the crystal of an unprecedented 2-alkyl-1,2,3-selenadiazolium salt have been unambiguously proved. NMR-spectroscopic data of proton, carbon, selenium, and nitrogen of this compound and its 3-methyl isomer are reported and compared. The similarity of these data is surprising. As the crystallographic and spectroscopic information is clearly reported, the chemistry of these salts must be explored.

4. Materials and Methods

Commercially available reagents were used without further purification unless otherwise indicated; solvents were dried by standard procedures. Yields refer to chromatographically and spectroscopically pure compounds unless otherwise stated. ¹H and ¹³C NMR spectra: Bruker AV 400 (400 MHz) and Bruker ARX 400 (400 MHz) (Bruker, Billerica, MA, USA). Assignments of proton and carbon signals are based on COSY, HSQC, and HMBC experiments. Chemical shifts are expressed as δ values in ppm; coupling constants are given in Hz. Melting points: Tottoli apparatus (Büchi, Flawil, Switzerland). IR spectra: Beckman Acculab 4 (KBr, Houston, TX, USA). FD-MS: Mat 95 (Finnigan, Washington, DC, USA). UV/Vis spectra: Perkin-Elmer Lambda 16 (PerkinElmer, Waltham, MA, USA).