Synthesis of Novel Azolo[1,2,3,5]thiatriazines

Elena V. Sadchikova; Vasiliy A. Bakulev; Wim Dehaen; Kristof Van Hecke; Koen Robeyns; Luc Van Meervelt; Vladimir S. Mokrushin; Albert Padwa

doi:10.1055/s-2004-830895

LETTER

Synthesis of Novel Azolo[1,2,3,5]thiatriazines

Elena V. Sadchikova^a, Vasiliy A. Bakulev*^a, Wim Dehaen*^b, Kristof Van Hecke^b, Koen Robeyns^b, Luc Van Meervelt^b, Vladimir S. Mokrushin^a, Albert Padwa^c
^a TOSLab, Urals State Technical University, 620002, Ekaterinburg, Russia
Fax: +7(343)3754135; e-Mail: bakulev@r66.ru;
^b Department of Chemistry, University of Leuven, 3001 Leuven, Belgium
Fax: +32(16)327439; e-Mail: wim.dehaen@chem.kuleuven.ac.be;
^c Department of Chemistry, Emory University, 1515 Pierce Drive, Atlanta GA 30322, USA
Fax: +1(404)7270283; e-Mail: chemap@emory.edu;

Abstract

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Abstract

The cycloaddition of diazoazoles with acylisothiocyanates has been found to result in the formation of a 1,2,3,5-thiatriazine ring. This new reaction was used to prepare novel 8-substituted 4-[benzoylimino-4H-imidazo(pyrazolo)][5,1-d]-[1,2,3,5]thiatriazines. The structures of the compounds prepared were carefully studied by X-ray diffraction, IR and NMR spectroscopy.

Key words

heterocycles - cycloadditions - diazo compounds - bicyclic compounds

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References

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All melting points are uncorrected. IR spectra were recorded on a Perkin Elmer 1600 Series FTIR spectrometer in KBr pellets. The ¹H NMR and ¹³C NMR spectra were recorded in [²H₆]DMSO solution with Bruker WR-300 and Bruker DRX-400 spectrometer, 300 MHz and 400 MHz for ¹H, 75 MHzand 100 MHz for ¹³C using TMS as internal standard.
Spectroscopic data for compound 4a: yield 84%; mp 146-148 °C. IR (KBr): ν_max = 589.4, 666.5, 718.7, 772.9, 840.9, 1063.8, 1163.9, 1238.5, 1309.8, 1376.3, 1421.5, 1447.1, 1523.3, 1574.1, 1641.9, 1717.0, 2974.8, 3099.6 cm^-1. ¹H NMR (300.13 MHz, DMSO-d ₆, 300 K): δ = 1.38 (t, J = 7.0 Hz, 3 H, OCH₂CH₃), 4.44 (q, J = 7.0 Hz, 2 H, OCH₂CH₃), 7.60-7.65 (m, 2 H, 3′,5′-H), 7.73-7.77 (m, 1 H, 4′-H), 8.27 (d, J = 7.3 Hz, 2 H, 2′,6′-H), 8.86 (s, 1 H, 6-H). ¹³C NMR (75.4 MHz, DMSO-δ₆, 300 K): δ = 15.02, 63.31, 115.96, 129.98, 131.19, 134.22, 135.47, 143.55, 146.66, 158.62, 160.86, 178.0. Anal. Calcd for C₁₄H₁₁N₅O₃S: C, 51.06; H, 3.37; N, 21.26; S, 9.74. Found: C, 51.10; H, 3.39; N, 21.30; S, 9.66.
Spectroscopic data for compound 4b: yield 88%; mp 140-142 °C. IR (KBr): ν_max = 547.5, 590.4, 649.5, 719.3, 809.7, 854.1, 949.7, 1018.9, 1049.6, 1175.9, 1225.7, 1276.0, 1321.8, 1381.3, 1464.9, 1521.5, 1593.8, 1643.7, 1725.1, 2931.4, 2985.1, 3062.6, 3121.9 cm^-1. ¹H NMR (400.13 MHz, DMSO-d ₆, 298 K): δ = 1.38 (t, J = 7.0 Hz, 3 H, OCH₂CH₃), 4.46 (q, J = 7.0 Hz, 2 H, OCH₂CH₃), 7.63-7.60 (m, 2 H, 3′,5′-H), 7.78-7.71 (m, 1 H, 4′-H), 8.40 (d, 2 H, J = 7.0 Hz, 2′,6′-H), 9.55 (s, 1 H, 6-H). ¹³C NMR (100.62 MHz, DMSO-d ₆, 298 K): δ = 14.2, 61.4, 129.0, 130.7, 132.1, 133.2, 134.1, 134.6, 134.7, 157.2, 160.2, 176.9. Anal. Calcd for C₁₄H₁₁N₅O₃S: C, 51.06; H, 3.37; N, 21.26; S, 9.74. Found: C, 51.03; H, 3.35; N, 21.21; S, 9.79.
Spectroscopic data for compound 4c: yield 76%; mp 144-146 °C. IR (KBr): ν_max = 1530, 1575, 1600, 1620, 1650, 2875, 2930, 2960, 3050, 3075 cm^-1. ¹H NMR (250.13 MHz, DMSO-d ₆, 298 K): δ = 2.88 (t, 3 H, J = 4.6 Hz, NHCH₃), 7.64-7.58 (m, 3 H, 3′,4′,5′-H), 8.41 (d, 2 H, J = 7.0 Hz, 2′,6′-H), 8.65 (q, 1 H, J = 4.6 Hz, NHCH₃), 9.55 (s, 1 H, 6-H). ¹³C NMR (100.62 MHz, DMSO-d ₆, 298 K): δ = 26.0, 129.0, 130.7, 131.6, 132.8, 133.3, 134.6, 137.7, 157.6, 159.8, 176.8. Anal. Calcd for C₁₃H₁₀N₆O₂S: C, 49.68; H, 3.21; N, 26.74; S, 10.20. Found: C, 49.70; H, 3.20; N, 26.77; S, 10.25.
Spectroscopic data for compound 4d: yield 68%; mp 120-121 °C. IR (KBr): ν_max = 1530, 1580, 1600, 1620, 1640, 2875, 2930, 2960, 3060, 3080 cm^-1. ¹H NMR (250.13 MHz, DMSO-d ₆, 298 K): δ = 1.95-1.81 (m, 4 H, 2 CH₂), 3.55-3.48 (m, 2 H, CH₂), 3.66-3.58 (m, 2 H, CH₂), 7.64-7.58 (m, 3 H, 3′,4′,5′-H), 8.40 (d, 2 H, J = 7.3 Hz, 2′,6′-H), 9.55 (s, 1 H, 6-H). ¹³C NMR (100.62 MHz, DMSO-d ₆, 298 K): δ = 23.7, 25.6, 46.0, 48.0, 128.5, 129.0, 130.6, 131.7, 133.3, 134.6, 140.9, 157.5, 159.6, 176.8. Anal. Calcd for C₁₆H₁₄N₆O₂S: C, 54.23; H, 3.98; N, 23.71; S, 9.05. Found: C, 54.33; H, 4.02; N, 23.67; S, 9.01.
Spectroscopic data for compound 4e: yield 78%; mp 132-134 °C. IR (KBr): ν_max = 1510, 1575, 1590, 1625, 1640, 2860, 2925, 2945 cm^-1. ¹H NMR (400.13 MHz, DMSO-d ₆, 298 K): δ = 1.50-1.48 (m, 2 H, CH₂), 1.67-1.59 (m, 4 H, 3 CH₂), 3.44-3.41 (m, 2 H, CH₂), 3.72-3.69 (m, 2 H, CH₂), 7.64-7.60 (m, 2 H, 3′,5′-H), 7.78-7.74 (m, 1 H, 4′-H), 8.41 (d, 2 H, J = 8.2 Hz, 2′,6′-H), 9.58 (s, 1 H, 6-H). ¹³C NMR (100.62 MHz, DMSO-d ₆, 298 K): δ = 23.9, 25.3, 26.2, 42.3, 47.4, 129.0, 130.6, 131.9, 132.0, 133.3, 134.6, 140.8, 157.4, 160.0, 176.7. Anal. Calcd for C₁₇H₁₆N₆O₂S: C, 55.42; H, 4.38; N, 22.81; S, 8.70. Found: C, 55.43; H, 4.34; N, 22.77; S, 8.74.
Spectroscopic data for compound 4f: yield 81%; mp 136-138 °C. IR (KBr): ν_max = 1510, 1575, 1590, 1630, 1650, 2875, 2935, 2950 cm^-1. ¹H NMR (400.13 MHz, DMSO-d ₆, 298 K): δ = 3.52-3.53 (m, 2 H, CH₂), 3.57-3.58 (m, 2 H, CH₂), 3.71-3.72 (m, 2 H, CH₂), 3.74-3.75 (m, 2 H, CH₂), 7.60-7.64 (m, 2 H, 3′,5′-H), 7.74-7.77 (m, 1 H, 4′-H), 8.41 (d, 2 H, J = 7.2 Hz, 2′,6′-H), 9.59 (s, 1 H, 6-H). ¹³C NMR (100.62 MHz, DMSO-d ₆, 298 K): δ = 42.1, 47.0, 66.0, 66.4, 129.0, 130.6, 132.1, 132.3, 133.3, 134.6, 139.7, 157.3, 160.2, 176.8. Anal. Calcd for C₁₆H₁₄N₆O₃S: C, 51.89; H, 3.81; N, 22.69; S, 8.66. Found: C, 51.95; H, 3.84; N, 22.55; S, 8.60.

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9

X-Ray Diffraction Study of 4a: Crystals were grown from EtOAc. All measurements were made on a Bruker SMART 6000 diffractometer equipped with a CCD detector using CuKα radiation (λ = 1.54178 Å). The crystal system of compound 5a (C₁₄H₁₁N₅O₃S, M = 329.34) is monoclinic, space group P2₁/c, a = 6.859 (1), b = 17.817 (3), c = 11.840 (2) Å, β = 99.79 (1)°, Z = 4, V = 1425.9 (4) Å³, D _c = 1.534 g/cm³, F(000) = 680, crystal size: 0.10 × 0.10 × 0.25 mm, µ(CuKα) = 2.248 mm^-1, T = 100 K, 12657 reflections collected, 2755 unique reflections, R _int = 0.074. Final R indices: R ₁ = 0.0423 for 2291 reflections with I>2σ(I) and R ₁ = 0.0500, wR ₂ = 0.1122 for all data. Crystallographic data (excluding structure factors) for this structure have been deposited with the Cambridge Crystallographic Data Centre. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (1223)336033; e-mail: deposit@ccdc.cam.ac.uk].

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