Whitby group

4-Methyl-N-(non-4-yn-1-yl)benzenesulfonamide; 1-Bromohex-1-yne ;DMF; K₂CO₃; CuSO₄.5H₂O; 1,10-phenanthroline; ether; MgSO₄ 

General procedure A (see below) with 4-Methyl-N-(non-4-yn-1-yl)benzenesulfonamide  (1.47 g, 5.0 mmol) and 1-Bromohex-1-yne (886 mg, 5.5 mmol).  Purification by column chromatography (SiO₂, hexane/Et₂O 4:1) gave the title compound as an orange oil (1.09 g, 59%).

General Procedure A:

A solution of the appropriate sulfonamide (1 eq.) and the appropriate bromide (1.1 eq.) in DMF (35 mL) was added to K₂CO₃ (2 eq.), CuSO₄.5H₂O (0.1 eq.) and 1,10-phenanthroline (0.2 eq.).  The reaction mixture was stirred at 65 °C for 16 h.  The reaction mixture was poured into water (200 mL) and extracted with ether (3 × 50 mL).  The organic extracts were combined, washed with water (2 × 100 mL), dried (MgSO₄), filtered and the solvent removed in vacuo to give the crude product, which was purified as described.

¹H NMR: d_H (400 MHz, CDCl₃) 7.79 (2H, d, J 8.5 Hz, H-17), 7.33 (2H, d, J 8.5 Hz, H‑18), 3.37 (2H, t, J 7.0 Hz, H-7), 2.45 (3H, s, H-20), 2.26 (2H, t, J 7.0 Hz, H-9), 2.22–2.09 (4H, m, H-3,12), 1.80 (2H, quin, J 7.0 Hz, H-8), 1.54–1.31 (8H, m, H‑4,5,13,14), 0.91 (3H, t, J 7.3 Hz, H-6 or H-15), 0.90 (3H, t, J 7.5 Hz, H-6 or H-15)

¹³C NMR: d_C(100 MHz, CDCl₃) 144.18 (C, C-19), 134.64 (C, C-16), 129.53 (2 × CH), 127.64 (2 × CH), 81.21 (C), 78.33 (C), 72.89 (C), 70.22 (C), 50.50 (CH₂, C-7), 31.10 (CH₂), 30.98 (CH₂), 27.43 (CH₂), 21.89 (CH₂), 21.81 (CH₂), 21.59 (CH₃, C-20), 18.37 (CH₂), 18.11 (CH₂), 15.90 (CH₂), 13.58 (CH₃), 13.55 (CH₃)

LRMS: (ES+) m/z 396.3 ([M+Na]⁺)

HRMS: (ES+) Calculated for C₂₂H₃₁NNaO₂S: 396.1968 Da, found: 396.1974 Da

IR: n_max (neat)/cm⁻¹ 2956 (w), 2930 (w), 2871 (w), 1597 (w), 1166 (s), 544 (s)

4-Methyl-N-(4-phenylbut-3-yn-1-yl)benzenesulfonamide;  (Bromoethynyl)trimethylsilane; DMF; K₂CO₃; CuSO₄.5H₂O; 1,10-phenanthroline; ether; MgSO₄ 

General procedure B (see below) with 4-Methyl-N-(4-phenylbut-3-yn-1-yl)benzenesulfonamide  (1.50 g, 5.0 mmol) and (Bromoethynyl)trimethylsilane (886 mg, 5.0 mmol).  Purification by column chromatography (SiO₂, hexane/Et₂O 4:1) gave the title compound as a yellow solid (930 mg, 47%).

General procedure B:

A solution of the appropriate bromide (1 eq.) and N,N‑dimethylethylenediamine (0.2 eq.) in dry toluene (20 mL) was added to the appropriate sulfonamide (1 eq.), K₃PO₄ (2 eq.) and CuI (0.05 eq.) in toluene (10.0 mL).  The reaction mixture was heated to reflux for 16 h.  The reaction mixture was filtered through a plug of silica using ether to elute and the solvent removed in vacuo to give the crude product, which was purified as described.

¹H NMR: d_H(300 MHz, CDCl₃) 7.81 (2H, d, J 8.1 Hz, H-13), 7.42–7.21 (7H, m, H‑9,10,11,14), 3.58 (2H, t, J 7.6 Hz, H-4), 2.74 (2H, t, J 7.6 Hz, H-5), 2.43 (3H, s, H-16), 0.16 (9H, s, H-3)

¹³C NMR: d_C (75 MHz, CDCl₃) 144.73 (C, C-15), 134.51 (C, C-12), 131.61 (2 × CH), 129.65 (2 × CH), 128.18 (2 × CH), 127.97 (CH, C-11), 127.77 (2 × CH), 123.17 (C, C-8), 94.41 (C, C-1), 85.19 (C), 82.55 (C), 73.75 (C), 50.11 (CH₂, C-4), 21.62 (CH₃, C-16), 19.30 (CH₂, C-5), 0.05 (CH₃, C-3)

LRMS: (ES+) m/z 418.2 ([M+Na]⁺)

IR: n_max (neat)/cm⁻¹ 2958 (w), 2156 (m), 1597 (w), 1168 (s), 838 (s), 659 (s), 542 (s)

General procedure B with 4-Methyl-N-(oct-3-yn-1-yl)benzenesulfonamide (1.40 g, 5.0 mmol) and (Bromoethynyl)trimethylsilane  (886 mg, 5.0 mmol).  Purification by column chromatography (SiO₂, hexane/Et₂O 4:1) gave the title compound as an orange oil (445 mg, 30%).

General procedure B:

A solution of the appropriate bromide (1 eq.) and N,N‑dimethylethylenediamine (0.2 eq.) in dry toluene (20 mL) was added to the appropriate sulfonamide (1 eq.), K₃PO₄ (2 eq.) and CuI (0.05 eq.) in toluene (10.0 mL).  The reaction mixture was heated to reflux for 16 h.  The reaction mixture was filtered through a plug of silica using ether to elute and the solvent removed in vacuo to give the crude product, which was purified as described.