Facile Access to 3,7-Dialkyltetrahydro-1H,5H-[1,2,4]triazolo[1,2-a][1,2,4]triazole-1,5-dithiones

Abstract

A simple single-step methodology was developed to synthesize 3,7-dialkyltetrahydro-1H,5H-[1,2,4]triazolo[1,2-a][1,2,4]triazole-1,5-dithiones in improved yields by acid-catalyzed reaction of thiosemicarbazide and aliphatic aldehydes in anhydrous ethanol at reflux temperature. The products were obtained in good to excellent yields. A plausible mechanism involving two successive intramolecular heterocyclizations of thiosemicarbazone has also been proposed. The synthesized compounds were characterized by spectroscopic methods and confirmed by using X-ray crystallography. These C-2 symmetric hexaheteroatomic fused heterocycles are expected to have exceptional applications.

Key words

triazolo[1,2-a][1,2,4]triazole-1,5-dithiones - thiosemicarbazide - aliphatic aldehydes

• References and Notes

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• 18 Synthesis of 3,7-Dibutyltetrahydro(1,2,4)triazolo(1,2-a)(1,2,4)triazole-1,5-dithione (Table 1, 4d): To a stirred solution of thiosemicarbazide 1 (0.138 g, 1.0 mM) in absolute EtOH (25 mL), butanal (0.75 mL, 1.3 mM) along with 1–2 drops of concd sulfuric acid was added. The mixture was heated under reflux for 18 h. On completion (TLC monitoring), the reaction mixture was cooled to r.t., and the precipitate was filtered and recrystallized from EtOH to afford 4d as a white solid; mp 186 °C; yield: 89%; R_f 0.68 (PE–EtOAc, 7:3). IR (KBr): 3390 (N–H), 2962 (Me C–H stretch), 1220 (C=S) cm^–1. ¹H NMR (300 MHz, DMSO-d ₆): δ = 10.64 (s, 2 H, NH), 5.62 (s, 1 H, SH), 6.01 (dt, J = 12.0, 0.6 Hz, 1 H, NCHN), 1.31–1.39 (m, 5 H, CH₂), 1.57–1.65 (m, 4 H, CH₂), 0.89 (t, J = 6.9 Hz, 3 H, Me). ¹³C NMR (75 MHz, DMSO-d ₆): δ = 185.9 (C=S), 76.1 (C–N), 33.9, 26.4, 21.3, 14.4 (aliphatic C). Anal. Calcd for C₁₂H₂₂N₄S₂: C, 50.31; H, 7.74; N, 19.56; S, 22.39. Found: C, 50.29; H, 7.76; N, 19.55; S, 22.40. HRMS: m/z [M] calcd for C₁₂H₂₂N₄S₂: 286.13; found: 286.11.
• 19 Structure Determination of (4d): C₁₂H₂₂N₄S₂, M _r = 286.5, colourless crystal, size 0.36 × 0.25 × 0.20 mm³, tetragonal space group P4₂ /n with Z = 4, a = 9.4550(7), c = 17.151(3) Å, V = 1533.2(3) ų; D _c = 1.241 Mg/m³, μ = 0.338 mm^–1, F(000) = 616. The intensity data were recorded using a Bruker SMART CCD area-detector diffractometer with graphite monochromated MoK_α radiation (λ = 0.71073 Å) at T = 130(2) K. 14427 reflections collected 2.4 > Θ > 27.9°; 1838 independent reflections I >2σ(I), R _int = 0.027. The structure was solved by direct methods,²¹ with full-matrix least squares refinement²¹ based on F ² and 83 parameters. All but H atoms were refined anisotropically, hydrogen atoms were clearly located from difference Fourier maps, refined at idealized positions riding on the carbon atoms with isotropic displacement parameters U_iso(H) = 1.2U_eq(C/N) or 1.5U_eq(Me) and C–H 0.98–1.00 Å and N–H 0.88 Å. Refinement converged at R1 = 0.032 [I >2σ(I)], wR2 = 0.088 (all data) and S = 1.03; min/max, F –0.29/0.35 e/ų.
• 20 CCDC 1063612 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 21 Sheldrick GM. Acta Crystallographica Section A 2008; 64: 112