Synthesis of 3-Pyrazolyl-1,2,4-Triazoles via One-Pot Multicomponent Reaction in Phosphoric Acid

Abstract

A high-yielding synthetic route towards pyrazolyl-[1,2,4]triazole derivatives has been developed via one-pot multicomponent reaction of polyfunctionalized triazoles, DMF–DMA, acetophenone, ethyl cyanoacetate, and/or 3-oxo-3-phenylpropanenitrile in ortho-phosphoric acid (85%). In the same manner, a new series of 2-triazolyl-tetrahydro-indazol-4-ones and pyrazolo[3,4-d]pyrimidines has been synthesized by reaction of triazoles, DMF–DMA and 1,3-cyclohexanediones and/or barbituric acid, respectively. The same products were prepared a classical manner via reaction of triazoles with the corresponding enaminones in ortho-phosphoric acid (85%).

Key words

pyrazolyl-[1,2,4]triazole - 2-triazolyl-tetrahydro-indazol-4-one - enaminone - multicomponent reaction - ortho-phosphoric acid

• References and Notes

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• 23 4-Amino-5-(3-p-tolyl-pyrazol-1-yl)-4H-[1,2,4]-triazole-3-thiol (4c) Yellow solid, Methd A: 68% yield, Method B: 71% yield, mp 185–186 °C. IR (ATR): ν_max = 3304, 3200, 3076, 3028, 2917, 1592 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 14.00 (s, 1 H, SH), 8.44 (d, J = 2.6 Hz, 1 H, CH_pyrazole), 7.83 (d, J = 7.9 Hz, 2 H, 2 CH_phenyl), 7.30 (d, J = 7.9 Hz, 2 H, 2 CH_phenyl), 7.11 (d, J = 2.6 Hz, 1 H, CH_pyrazole), 5.81 (s, 2 H, NH₂), 2.35 (s, 3 H, CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 167.1, 154.0, 145.3, 138.7, 134.4, 129.8, 129.3, 126.2, 105.9, 21.3. Anal. Calcd for C₁₂H₁₂N₆S (272): C, 52.93; H,4.44; N, 30.86. Found: C, 52.99; H, 4.39; N, 30.76.
• 24 Ethyl 3-Amino-1-(4-amino-5-mercapto-4H-[1,2,4]-triazol-3-yl)-1H-pyrazole-4-carboxylate (6a) Yellow solid, Method A: 61% yield, Method B: 61% yield, mp 119–120 °C. IR (ATR): ν_max = 3431, 3318, 3259, 3176, 3112, 2983, 2959, 2904, 1683, 1631 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 14.09 (s, 1 H, SH), 7.78 (s, 1 H, CH_pyrazole), 6.85 (s, 2 H, NH₂), 5.48 (s, 2 H, NH₂), 4.22 (q, J = 7.0 Hz, 2 H, CH₂), 1.28 (t, J = 7.0 Hz, 3 H, CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 167.8, 163.3, 153.3, 143.4, 142.9, 93.5, 59.5, 14.9. Anal. Calcd for C₈H₁₁N₇O₂S (269): C, 35.68; H,4.12; N, 36.41. Found: C, 35.69; H, 4.10; N, 36.45.
• 25 2-(4-Amino-5-mercapto-4H-[1,2,4]triazol-3-yl)-6,6-dimethyl-2,5,6,7-tetrahydro-indazol-4-one (7b) Yellow solid, Method A: 78% yield, Method B: 84% yield, mp 249–251 °C. IR (ATR): ν_max = 3300, 3200, 3166, 2957, 2930, 2870, 1674 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 14.23 (s, 1 H, SH), 8.18 (s, 1 H, CH_pyrazole), 5.72 (s, 2 H, NH₂), 2.83 (s, 2 H, CH₂), 2.40 (s, 2 H, CH₂), 1.06 (s, 6 H, 2 CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 192.2, 168.2, 153.9, 143.9, 139.8, 119.4, 52.0, 35.8, 34.5, 28.0. Anal. Calcd for C₁₁H₁₄N₆OS (278): C, 47.47; H,5.07; N, 30.19. Found: C, 47.48; H, 5.00; N, 30.09.