Yield:1162-56-7 50% ，25093-47-4 4%

Reaction Conditions:

with chloranil in tert-butyl alcohol at 20; for 1 h;

Steps:

31 2.2.31 Oxidation of progesterone by chloranil

To a solution of progesterone (2.44 g, 7.8 mmol) in tert-butanol (170 mL) was added chloranil (4.6 g, 18.7 mmol) at room temperature. The reaction mixture was heated to reflux for one hour then cooled down to room temperature and filtered. The precipitate was washed with chloroform. Combined filtrates were concentrated in vacuo and the residue was diluted in chloroform (200 mL). Organic phase was successively washed with water (3 * 20 mL), 1.2 M NaOH aqueous solution (4 * 20 mL) then with water (4 * 20 mL). The organic phase was dried over Na₂SO₄, filtered through Whatman No.4 paper and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (ACOEt/cyclohexane, 1:2) to give compound 35a as a white solid (1.23 g, 50% yield) and trace amounts of epimer 35b (0.01 g, 4% yield). 2.2.31.1 Δ⁶-Progesterone (35a)[9,31] Mp = 144-145 °C (Litt 144-145 °C) [9] ; ¹H NMR (CDCl₃) δ: 6.10 (m, 2H, H-6 et H-7), 5.67 (s, 1H, H-4), 2.64-2.51 (m, 2H), 2.42 (m, 1H), 2.29-1.10 (m, 13H), 2.12 (s, 3H, CH₃-21), 1.10 (s, 3H, CH₃-19), 0.70 (s, 3H, CH₃-18) ppm; ¹³C NMR (CDCl₃) δ: 209.15 (C-20), 199.58 (C-3), 163.53 (C-5), 140.64 (CH-7), 128.26 (CH-6), 123.92 (CH-4), 63.37 (CH-17), 53.79 (CH), 50.68 (CH), 44.84 I, 38.69 (CH₂), 37.72 (CH), 36.16 I, 34.03 (2 * CH₂), 31.64 (CH₃-21), 24.02(CH₂), 23.02 (CH₂), 20.76 (CH₂), 16.42 (CH₃-19), 13.39 (CH₃-18) ppm. 2.2.31.2 17α-Δ⁶-Progesterone (35b). Mp = 137-139 °C. ¹H NMR (CDCl₃) δ: 6.10 (dd, 1H, J1 = 9.8 Hz, J2 = 1.5 Hz, H-6), 6.05 (dd, 1H, J1 = 9.8 Hz, J2 = 2.5 Hz, H-7), 5.62 (s, 1H, H-4), 2.82 (dd, 1H, J1 = 8.3 Hz, J2 = 2.0 Hz, H-17), 2.60-2.42 (m, 1H), 2.60-2.42 (m, 1H), 2.39-2.29 (m, 1H), 2.15-1.10 (m, 13H), 2.10 (s, 3H, CH₃-21), 1.06 (s, 3H, CH₃-19), 0.96 (s, 3H, CH₃-18) ppm; ¹³C NMR (CDCl₃) δ: 212.45 (C-20), 199.48 (C-3), 163.59 (C-5), 141.28 (CH-7), 127.87 (CH-6), 123.69 (CH-4), 60.77 (CH-17), 50.05 (CH), 47.48 (CH), 46.33 I, 37.79 (CH), 36.03 I, 34.92 (CH₂), 33.96 (CH₂), 33.92 (CH₂), 32.95 (CH₃-21), 25.29 (CH₂), 24.48 (CH₂), 20.62 (CH₃-18 + CH₂), 16.36 (CH₃-19) ppm; MS (ESI): m/z (%) 647 (100) [2M+Na]⁺, 335 (18) [M+Na]⁺, 313 (65) [M+H]⁺; HRMS (ESI): m/z: calc for C₂₁H₂₈O₂ + H: 313.2162, found: 313.2154.

References:

Zeinyeh, Wael;Mahiout, Zahia;Radix, Sylvie;Lomberget, Thierry;Dumoulin, Axel;Barret, Roland;Grenot, Catherine;Rocheblave, Luc;Walchshofer, Nadia;Matera, Eva-Laure;Dumontet, Charles [Steroids,2012,vol. 77,# 12,p. 1177 - 1191,15]