A Simple, Advantageous Synthesis of 5-Substituted 1H-Tetrazoles [¹]

Abstract

An advantageous synthesis of 5-substituted 1H-tetrazoles has been developed by treatment of organic nitriles with NaN₃ in the presence of iodine or the heterogeneous catalyst, silica-­supported sodium hydrogen sulfate (NaHSO₄˙SiO₂).

Key words

5-substitued 1H-tetrazole - organic nitrile - NaN₃ - NaHSO₄˙SiO₂ - [3+2] cycloaddition - heterogeneous conditions

1

Part 189 in the series ‘Studies on novel synthetic methodologies’.

References and Notes

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1

Part 189 in the series ‘Studies on novel synthetic methodologies’.

13

Typical experimental procedure using NaHSO ₄ ˙SiO ₂ : To a mixture of benzonitrile (2.0 mmol) and NaN₃ (3.0 mmol) in DMF (5 mL), NaHSO₄˙SiO₂ (0.09 g) was added. The mixture was stirred at 120 ˚C for 10 h until the reaction was complete (reaction monitored by TLC). The catalyst was removed by filtration and washed with EtOAc (2 × 5 mL). The filtrate was treated with EtOAc (30 mL) and 4 M HCl (20 mL) and stirred vigorously. The organic layer was separated and the aqueous layer was extracted with EtOAc (2 × 10 mL). The combined organic extracts were washed with H₂O (2 × 10 mL) and concentrated. The crude product was subjected to column chromatography (silica gel; hexane-EtOAc) to obtain pure 5-phenyl tetrazole (91%). Typical experimental procedure using I ₂ : To a mixture of benzonitrile (2.0 mmol) and NaN₃ (3.0 mmol) in DMF (5 mL), I₂ (0.03 g) was added and the mixture was stirred at 120 ˚C. After completion of the reaction (10 h), the mixture was treated with EtOAc (30 mL) and 4 M HCl (20 mL) and stirred vigorously. The organic layer was separated and the aqueous layer was extracted with EtOAc (2 × 10 mL). The combined organic portion was washed with saturated sodium thiosulfate solution (2 × 10 mL) and H₂O (2 × 10 mL) and subsequently concentrated. The residue was purified by column chromatography (silica gel; hexane-EtOAc) to afford pure 5-phenyl tetrazole (89%).
Spectroscopic data of representative novel compounds: 2c: IR: 3442, 1598, 1563,1484, 1411 cm^-¹; ^¹H NMR (200 MHz, DMSO-d ₆): δ = 7.91 (1 H, br s), 7.84 (1 H, d, J = 8.0 Hz), 7.40 (1 H, t, J = 8.0 Hz), 7.30 (1 H, d, J = 8.0 Hz), 2.45 (3 H, s); ^¹³C NMR (50 MHz, DMSO-d ₆): δ = 155.7, 138.6, 131.1, 128.2, 127.4, 123.8, 20.2; MS (ESI): m/z = 161 [M + H]⁺; HRMS (ESI): m/z [M + H]⁺ calcd for C₈H₉N₄: 161.0827; found: 161.0830. 2d: IR: 3477, 1663, 1603, 1515, 1317 cm^-¹; ^¹H NMR (200 MHz, DMSO-d ₆): δ = 7.30 (2 H, d, J = 8.0 Hz), 6.62 (2 H, d, J = 8.0 Hz), 5.43 (2 H, br s); ^¹³C NMR (50 MHz, DMSO-d ₆): δ = 157.6, 151.2, 132.1, 119.0, 112.2; MS (ESI): m/z = 162 [M + H]⁺; Anal. Calcd for C₇H₇N₅: C, 52.17; H, 4.35; N, 3.11. Found: C, 52.28; H, 4.29; N, 3.17. 2h: IR: 3507, 1709, 1564, 1431, 1286 cm^-¹; ^¹H NMR (200 MHz, DMSO-d ₆): δ = 8.20 (2 H, d, J = 8.0 Hz), 8.11 (2 H, d, J = 8.0 Hz), 3.91 (3 H, s); ^¹³C NMR (50 MHz, DMSO-d ₆):
δ = 155.8, 132.2, 131.2, 130.0, 129.1, 126.3, 51.4; MS (ESI): m/z = 205 [M + H]⁺; HRMS (ESI): m/z [M + H]⁺ calcd for C₉H₉N₄O₂: 205.0725; found: 205.0735. 2k: IR: 3453, 1628, 1527, 1482 cm^-¹; ^¹H NMR (200 MHz, DMSO-d ₆): δ = 9.42 (1 H, d, J = 8.0 Hz), 8.41 (1 H, d, J = 8.0 Hz), 7.56 (1 H, t, J = 8.0 Hz); ^¹³C NMR (50 MHz, DMSO-d ₆): δ = 155.8, 147.1, 140.6, 131.0, 128.2, 127.1; MS (ESI): m/z = 182, 183 [M + H]⁺; Anal. Calcd for C₆H₄ClN₅: C, 39.67; H, 2.20; N, 38.57. Found: C, 39.78; H, 2.14; N, 38.63. 2n: IR: 3426, 1648, 1237 cm^-¹; ^¹H NMR (200 MHz, DMSO-d ₆): δ = 10.46 (1 H, br s), 4.50 (2 H, q, J = 7.0 Hz), 1.42 (3 H, t, J = 7.0 Hz); ^¹³C NMR (50 MHz, DMSO-d ₆): δ = 157.1, 151.6, 54.6, 14.8; MS (ESI): m/z = 143 [M + H]⁺; Anal. Calcd for C₄H₆N₄O₂: C, 33.80; H, 4.23; N, 39.44. Found: C, 33.91; H, 4.28; N, 39.37.