Transformations of 1-(Oxiranylmethyl)-1,2,3-triazoles into 2-(Oxiranyl­methyl)-1,2,3-triazoles and Alkanenitriles

Abstract

New reactions for the transformation of 1-(oxiranylmethyl)-1,2,3-triazoles into 2-(oxiranylmethyl)-1,2,3-triazoles or alkanenitriles were established. Successive treatment of the substrate with triflic acid and t-BuOH afforded 4,6-dihydro-5-hydroxy-1,3a,6a-triazapentalene derivative. Under the influence of NaH, the bicyclic compound was converted into a 2-(oxiranylmethyl)-1,2,3-triazole or an alkanenitrile. The reaction pathway depends on the substituent pattern of the epoxide side chain.

Key words

1,2,3-triazole - 2-substituted 1,2,3-triazole - click reaction

• References and Notes

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• 7 One-pot click reaction of alkyl halide, see: Kacprzak K. Synlett 2005; 943
• 8 4-Tridecyl triazole 5a was employed for the structural analysis of the reactive intermediate cation 8a because corresponding butyl or phenyl compounds are insoluble amorphous materials in CDCl₃.
• 9 Other Brønsted and Lewis acids such as BF₃·OEt₂, Et₂AlCl, TiCl₄, Hg(OTf)₂, and TFA could not activate the epoxide. However, TBSOTf and TMSOTf also gave the intermediate 8a due to in situ generated TfOH.
• 10 We confirmed that the internal 1,2,3-triazole ring is necessary for the ring-opening reaction of oxirane leading to triflate alcohol 8. Treatment of oxirane 15 with TfOH (2.0 equiv) gave a complex mixture. Similar treatment in the presence of triazole 16 (1 equiv) also afforded the complex mixture (Scheme 4).
• 11 Treatment of 5a with sodium hydride induced the ring-opening reaction of epoxide to give the corresponding enamino alcohol 17 in 23% yield (Scheme 5), along with recovery of starting material 5a (70%).
• 12a The comparison of halogen atoms in the epoxide ring-closing reaction of 2,2,6,6-tetrahalogenocyclohexanols, see: Duhamel P, Leblond B, Bidois-Séry L, Poirier J.-M. J. Chem. Soc., Perkin Trans. 1 1994; 16: 2265
• 12b Epoxide-forming reaction of 2-chloro-1-(1-chlorocyclopropyl)ethanol, see: Sudo K, Shimokawara T, Imai E, Kusano N, Kanno H, Miyake T, Mori M, Saishoji T. WO 2011070742, 2011
• 13 Typical Procedure for the Transformation of 5a into Nitrile 10To a solution of 5a (43 mg, 0.14 mmol) in CH₂Cl₂ (0.7 mL) was added TfOH (25 μL, 0.28 mmol) at 0 °C. After the mixture was stirred at r.t. for 30 min, t-BuOH (1 mL) was added. The mixture was stirred for 3 h and concentrated under reduced pressure to give crude 9a. To a suspension of NaH (21 mg, 0.49 mmol) in THF (0.5 mL) was added a solution of crude 9a in THF (2.3 mL) through a cannula at 0 °C. The mixture was stirred for 3.5 h, and the reaction was quenched with sat. aq NH₄Cl solution. The mixture was extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over MgSO₄, filtered, and concentrated under reduced pressure. The residue was purified by flash silica gel column chromatography (hexane–EtOAc, 4:1) to give nitrile 10 (22 mg, 70%) as a colorless oil. Compound 9a: ¹H NMR (500 MHz, CDCl₃): δ = 8.13 (s, 1 H), 5.47 (br, 1 H), 4.92 (dd, J = 14.0, 4.9 Hz, 1 H), 4.86 (dd, J = 13.2, 5.2 Hz, 1 H), 4.72 (d, J = 13.7 Hz, 1 H), 4.64 (d, J = 13.2 Hz, 1 H), 2.76 (t, J = 8.0 Hz, 2 H), 1.70–1.64 (m, 2 H), 1.36–1.26 (m, 20 H), 0.87 (t, J = 6.9 Hz, 3 H).
• 14 The transformation of 1-(oxiranylmethyl)-1,2,3-triazoles 5 into 2-(oxiranylmethyl)-1,2,3-triazoles 6 is conducted in the same manner as the above-mentioned typical procedure.Compound 6e: white amorphous solid. ¹H NMR (500 MHz, CDCl₃): δ = 7.38 (s, 1 H), 4.55 (dd, J = 14.4, 6.3 Hz, 1 H), 4.48 (dd, J = 14.3, 6.3 Hz, 1 H), 3.23 (t, J = 6.0 Hz, 1 H), 2.66 (t, J = 7.7 Hz, 2 H), 1.68–1.62 (m, 2 H), 1.43 (s, 3 H), 1.36 (s, 3 H), 1.34–1.26 (m, 20 H), 0.88 (t, J = 6.9 Hz, 4 H). ¹³C NMR (125.8 MHz, CDCl₃): δ = 149.20, 133.00, 60.86, 58.65, 53.92, 31.88, 29.64, 29.62, 29.61, 29.59, 29.51, 29.32, 29.23, 29.21, 25.44, 24.37, 22.65, 18.86, 14.08. HRMS (EI): m/z calcd for: 335.2936 [M⁺]; found: 335.2946.Compound 6g: ¹H NMR (500 MHz, CDCl₃): δ = 7.86 (s, 1 H), 7.77 (d, J = 6.9 Hz, 2 H), 7.41 (t, J = 7.4 Hz, 2 H), 7.34 (t, J = 7.4 Hz, 1 H), 4.64 (dd, J = 14.3, 5.7 Hz, 1 H), 4.54 (dd, J = 14.3, 5.7 Hz, 1 H), 3.29 (t, J = 5.7 Hz, 1 H), 1.46 (s, 3 H), 1.36 (s, 3 H).Compound 6h: ¹H NMR (500 MHz, CDCl₃): δ = 7.54 (s, 1 H), 4.51 (dd, J = 13.8, 5.8 Hz, 1 H), 4.48 (s, 2 H), 4.47 (dd, J = 14.3, 5.7 Hz, 1 H), 3.34 (s, 3 H), 3.18 (t, J = 5.7 Hz, 1 H), 1.37 (s, 3 H), 1.29 (s, 3 H), 1.36 (s, 3 H).Compound 6i: ¹H NMR (500 MHz, CDCl₃): δ = 7.37 (s, 1 H), 7.34–7.27 (m, 5 H), 4.53 (dd, J = 14.3, 5.8 Hz, 1 H), 4.52 (s, 2 H), 4.48 (dd, J = 14.3, 5.8 Hz, 1 H), 3.53 (t, J = 6.3 Hz, 2 H), 3.22 (t, J = 5.8 Hz, 1 H), 2.79 (t, J = 5.7 Hz, 2 H), 1.98 (quin, J = 6.3 Hz, 2 H), 1.43 (s, 3 H), 1.36 (s, 3 H).Compound 6j: ¹H NMR (500 MHz, CDCl₃): δ = 7.36 (s, 1 H), 4.47 (dd, J = 14.3, 5.8 Hz, 1 H), 4.44 (dd, J = 14.3, 5.7 Hz, 1 H), 3.52 (t, J = 6.3 Hz, 2 H), 3.16 (t, J = 5.7 Hz, 1 H), 2.79 (t, J = 6.9 Hz, 2 H), 2.08 (quin, J = 6.3 Hz, 2 H), 1.36 (s, 3 H), 1.30 (s, 3 H)