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DOI: 10.1055/s-2006-939708
An Efficient Access to 4-Alkylidene-5,6-dihydro-4H-pyrrolo[1,2-c][1,2,3]triazoles
Publication History
Publication Date:
26 April 2006 (online)
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Abstract
From alkylidenecyclopropanes (MCPs), 4-alkylidene-5,6-dihydro-4H-pyrrolo-[1,2-c][1,2,3]triazoles 6 were prepared in moderate yields through diiodogenation, Cu(I)-catalyzed 1,3-dipolar cycloaddition and subsequent intramolecular Heck reaction.
Key words
1,2,3-trizaole - alkylidenecyclopropanes (MCPs) - 1,3-dipolar cycloaddition - Heck reaction
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References and Notes
Typical Procedure for the Synthesis of 5.
To a stirred 95% EtOH (2 mL) solution of NaN3 (0.6 mmol), 2 (0.5 mmol) was added and the reaction mixture was stirred under reflux until the reaction was complete, as monitored by TLC. Then, H2O (4 mL), ascorbic acid (0.1 g, 0.56 mmol), NaOH (0.022 g, 0.56 mmol), CuSO4 (0.01 g, 0.04 mmol), and alkyne 4 (0.6 mmol) were added and heated together at 70 °C until the reaction was complete (monitored by TLC). Afterwards, the mixture was cooled to r.t. and H2O (15 mL) was added. The aqueous layer was extracted with EtOAc (3 × 15 mL). The organic layer was dried over anhyd MgSO4. After evaporation, the residue was subjected to preparative TLC (eluent: PE-EtOAc, 1:6 to 1:3) to afford 1,4-disub-stituted 1,2,3-triazoles 5.
Selected Spectral Data for 5a.
Solid, mp 70-72 °C. 1H NMR (400 MHz, CDCl3): δ = 0.95 (t, 3 H, J = 7.33 Hz), 1.39-1.44 (m, 2 H), 1.64-1.71 (m, 2 H), 2.74 (t, 2 H, J = 7.66 Hz), 3.08 (t, 2 H, J = 6.41 Hz), 4.58 (t, 2 H, J = 6.41 Hz), 6.75 (dd, 2 H, J = 1.75, 7.79 Hz), 7.10-7.32 (m, 9 H). 13C NMR (100 MHz, CDCl3): δ = 152.17, 148.27, 146.08, 139.29, 128.50, 128.24, 127.91, 127.60, 127.56, 121.04, 102.68, 49.67, 42.45, 31.77, 25.32, 22.35, 13.85. IR: 2955, 2926, 1437, 1043, 701 cm-1.
The temperature (70 °C) is required for the triazole synthesis step in our reaction by trial and error. At higher temperature 1,5-regioisomers can be formed and at lower temperature the reaction was not complete after several hours.
11
Typical Procedure for the Synthesis of 6.
Compound 5 (0.25 mmol), Pd(OAc)2 (0.025 mmol), tetrabutylammonium chloride (TBAC, 0.25 mmol), NaHCO3 (0.5 mmol), and N,N-dimethylformamide (DMF, 1 mL) were added into a Schlenk tube at r.t. The reaction mixture was stirred at 100 °C until the reaction was complete, as monitored by TLC. Then the reaction mixture was cooled and H2O (15 mL) was added. The aqueous layer was extracted with EtOAc (3 ¥ 15 mL). The organic layer was dried over anhyd MgSO4. After evaporation, the residue was subjected to preparative TLC (eluent: PE-EtOAc, 1:6 to 1:3) to afford 4-alkylidene-5,6-dihydro-4H-pyrrolo-[1,2-c][1,2,3]-triazoles 6.
Selected Data.
Compound 6a: solid, mp 124-126 °C. IR: 2948, 2924, 1440, 764, 703 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.74 (t, 3 H, J = 7.26 Hz), 0.92-1.00 (m, 2 H), 1.20-1.28 (m, 2 H), 1.49 (t, 2 H, J = 7.45 Hz), 3.51 (t, 2 H, J = 6.89 Hz), 4.36 (t, 2 H, J = 6.89 Hz), 7.18-7.38 (m, 10 H). 13C NMR (100 MHz, CDCl3): δ = 141.97, 141.94, 141.30, 138.43, 137.67, 129.92, 129.18, 128.72, 128.21, 127.86, 127.70, 123.51, 45.24, 37.50, 31.62, 25.35, 22.28, 13.76. MS (EI, 70 eV): m/z (%) = 329 (19) [M+]. Anal. Calcd for C22H23N3: C, 80.21; H, 7.04; N, 12.76. Found: C, 80.00; H, 7.16; N, 12.83.
Compound 7a: solid, mp 126-128 °C. IR: 2926, 1486, 1086, 828 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.91 (t, 3 H, J = 7.33 Hz), 1.34-1.40 (m, 2 H), 1.61-1.68 (m, 2 H), 2.73 (t, 2 H, J = 7.58 Hz), 2.99 (t, 2 H, J = 6.71 Hz), 4.54 (t, 2 H, J = 6.71 Hz), 7.27 (s, 4 H), 7.40 (s, 1 H). 13C NMR (100 MHz, CDCl3): δ = 148.35, 134.24, 132.75, 128.61, 121.27, 120.96, 86.01, 82.23, 48.65, 31.55, 25.28, 22.22, 21.63, 13.78. MS (EI, 70 eV): m/z (%) = 287 (29.08) [M+]. Anal. Calcd for C16H18ClN3: C, 66.78; H, 6.30; N, 14.60. Found: C, 66.90; H, 6.21; N, 14.65.