2.2. General Procedure for the Bis(spiroazetidinones) 6 and 7 Synthesis
The mixture of zinc (3.0 g, 46 mmol), methyl 1-bromocycloalkanecarboxylate (12 mmol), HgCl2 (5 mg), and N,N′-bis(arylmethylidene)benzidine 3 (5 mmol) in dry toluene (20 mL) with 2 mL of HMPA was heated for 4 h under reflux and then cooled down, decanted from the zinc excess, and treated with 5% acetic acid. Organic layer was separated, and the aqueous layer was twice extracted with ethyl acetate. The combined organic layers were dried over Na2SO4 and then concentrated. The residue was purified by the recrystallization from p-xylene to give the reaction products 6a–i and 7a–k as white or Slightly colored Solids.
2.2.1. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-phenyl-2-azaspiro[3.4]octan-1-one) (6a)
Yield: 1.88 g (68%), m.p. 296–299°C. IR (ν, cm−1): 1729 (CO). 1H-NMR (δ, ppm): 1.20–2.29 m [16H, 2 (CH2)4], 4.89 s (2H, 2 CH), 7.22–7.37 m (10H, 2 Ph), 7.33 d, and 7.40 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 25.33, 25.70, 28.99, 35.05, and 66.44 (Ccyclopentane); 67.62 (CH); 117.76, 126.88, 127.41, 127.80, 128.38, 134.83, 136.31, and 137.07 (CAr); 171.81 (CO). Anal. Calc. for C38H36N2O2: C, 82.58; H, 6.57; and N, 5.07. Found: C, 82.40; H, 6.67; and N, 4.99.
2.2.2. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(p-tolyl)-2-azaspiro[3.4]octan-1-one) (6b)
Yield: 2.44 g (84%), m.p. 234–236°C. IR (ν, cm−1): 1737 (CO). 1H-NMR (δ, ppm): 1.21–2.28 m [16H, 2 (CH2)4], 2.36 s (6H, 2 Me), 4.86 s (2H, 2 CH), 7.11 d, 7.17 d [8H, 2 (4-MeC6H4), J = 8.0 Hz], 7.34 d, and 7.39 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 21.26 (Me), 25.32, 25.67, 28.94, 34.97, and 66.27 (Ccyclopentane); 67.50 (CH); 117.72, 126.78, 127.31, 129.18, 129.66, 133.16, 137.07, and 138.08 (CAr); 171.85 (CO). Anal. Calc. for C40H40N2O2: C, 82.72; H, 6.94; and N, 4.82. Found: C, 82.89; H, 7.03; and N, 4.73.
2.2.3. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(4-methoxyphenyl)-2-azaspiro[3.4]octan-1-one) (6c)
Yield: 1.81 g (59%), m.p. 284–286°C. IR (ν, cm−1): 1737 (CO). 1H-NMR (δ, ppm): 1.19–2.26 m [16H, 2 (CH2)4], 3.80 s (6H, 2 MeO), 4.84 s (2H, 2 CH), 6.90 d, 7.15 d [8H, 2 (4-MeOC6H4), J = 8.8 Hz] 7.33 d, and 7.40 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 25.36, 25.71, 28.70, 34.98, and 67.37 (Ccyclopentane); 55.41 (MeO) and 66.39 (CH); 117.78, 127.37, 128.10, 129.06, 134.82, 135.88, 137.10, and 159.74 (CAr); 171.93 (CO). Anal. Calc. for C40H40N2O4: C, 78.40; H, 6.58; and N, 4.57. Found: C, 78.48; H, 6.42; and N, 4.65.
2.2.4. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(3,4-dimethoxyphenyl)-2-azaspiro[3.4]octan-1-one) (6d)
Yield: 2.25 g (67%), m.p. 248–250°C. IR (ν, cm−1): 1733 (CO). 1H-NMR (δ, ppm): 1.24–2.26 m [16H, 2 (CH2)4], 3.80 s (6H, 2 MeO), 3.87 s (6H, 2 MeO), 4.82 s (2H, 2 CH), 6.70 d (J 2.0 Hz), 6.79 dd (J = 8.4 Hz, J = 2.0 Hz), 6.86 d (J = 8.4 Hz) [6H, 2 (3,4-MeO)2C6H3)], 7.33 d, and 7.40 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 25.48, 25.75, 28.99, 35.04, and 67.65 (Ccyclopentane); 56.08 (MeO), 56.22 (MeO), and 66.40 (CH); 109.98, 111.74, 117.77, 119.46, 127.33, 128.74, 135.85, 137.12, 149.24, and 149.62 (CAr); 171.98 (CO). Anal. Calc. for C42H44N2O4: C, 74.98; H, 6.59; and N, 4.16. Found: C, 75.23; H, 6.42; and N, 4.31.
2.2.5. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(benzo[d][1,3]dioxol-5-yl)-2-azaspiro[3.4]octan-1-one) (6e)
Yield: 2.02 g (63%), m.p. 289–292°C. IR (ν, cm−1): 1732 (CO). 1H-NMR (δ, ppm): 1.25–2.30 m [16H, 2 (CH2)4], 4.80 s (2H, 2 CH), 5.96 dd (4H, 2 OCH2O, J = 4.4 Hz, J = 1.6 Hz), 6.69 d, 6.71 dd, 6.80 d [6H, 2 (3,4-OCH2OC6H3), J = 8.0 Hz, J = 1.6 Hz], 7,33 d, and 7.41 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 25.44, 25.72, 28.94, 35.01, and 67.50, (Ccyclopentane); 66.46 (CH); 101.43 (OCH2O); 107.08, 108.76, 117.74, 120.44, 127.41, 130.18, 135.94, 137.00, 147.79, and 148.42 (CAr); 171.80 (CO). Anal. Calc. for C40H36N2O6: C, 74.98; H, 5.66; and N, 4.37. Found: C, 75.14; H, 5.48; and N, 4.31.
2.2.6. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(4-fluorophenyl)-2-azaspiro[3.4]octan-1-one) (6f)
Yield: 1.74 g (59%), m.p. 298–300°C. IR (ν, cm−1): 1740 (CO). 1H-NMR (δ, ppm): 1.16–2.28 m [16H, 2 (CH2)4], 4.88 s (2H, 2 CH), 7.07 t, 7.21 t [8H, 2 (4-FC6H4), J = 8.4 Hz] 7.31 d, and 7.41 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 25.29, 25.67, 29.00, 34.96, and 66.49 (Ccyclopentane); 66.94 (CH); 116.00, 116.22, 117.73, 127.46, 127.48, 128.49, 129.07, 135.98, 136.01, 136.91, 161.54, and 164.00 (CAr); 171.63 (CO). 19F-NMR (δ, ppm): −114.59. Anal. Calc. for C38H34F2N2O2: C, 77.53; H, 5.82; and N, 4.76. Found: C, 77.71; H, 5.92; and N, 4.59.
2.2.7. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(4-chlorophenyl)-2-azaspiro[3.4]octan-1-one) (6g)
Yield: 1.68 g (54%), m.p. 274–276°C. IR (ν, cm−1): 1746 (CO). 1H-NMR (δ, ppm): 1.17–2.30 m [16H, 2 (CH2)4], 4.87 s (2H, 2 CH), 7.17 d, 7.30 d [8H, 2 (4-ClC6H4), J = 8.8 Hz], 7.35 d, and 7.41 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 25.28, 25.64, 29.01, 34.96, and 66.53 (Ccyclopentane); 66.90 (CH); 117.69, 127.47, 128.22, 129.32, 134.30, 134.89, and 136.03, 136.84 (CAr); 171.48 (CO). Anal. Calc. for C38H34Cl2N2O2: C, 73.43; H, 5.51; Cl, 11.41; and N, 4.51. Found: C, 73.21; H, 5.34; Cl, 11.59; and N, 4.33.
2.2.8. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(2,4-dichlorophenyl)-2-azaspiro[3.4]octan-1-one) (6h)
Yield: 2.31 g (67%), m.p. 264–267°C. IR (ν, cm−1): 1743 (CO). 1H-NMR (δ, ppm): 1.11–2.35 m [16H, 2 (CH2)4], 5.31 s (2H, 2 CH), 7.10 d (J = 8.4 Hz), 7.21 dd (J = 8.4 Hz, J = 2.0 Hz), 7.49 d (J = 2.0 Hz), [6H, 2 (2,4-Cl2C6H3)], 7,30 d, and 7.44 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 25.89, 26.07, 29, 59, 34.37, and 66.19 (Ccyclopentane); 63.18 (CH); 117.65, 127.60, 127.81, 128.80, 129.95, 132.81, 134.02, 134.60, 136.14, and 136.68 (CAr); 171.91 (CO). Anal. Calc. for C38H32Cl4N2O2: C, 66.10; H, 4.67; Cl, 20.54; and N, 4.06. Found: C, 66.23; H, 4.83; Cl, 20.22; and N, 4.01.
2.2.9. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(4-(dimethylamino)phenyl)-2-azaspiro[3.4]octan-1-one) (6i)
Yield: 2.52 g (79%), m.p. 265–268°C. IR (ν, cm−1): 1738 (CO). 1H-NMR (δ, ppm): 1.25–2.25 m [16H, 2 (CH2)4], 2.97 s (12H, 2 Me2N), 4.81 s (2H, 2 CH), 6.79 b, 7.10 d [8H, 2 (4-Me2NC6H4), J = 8.4 Hz], 7.33 d, and 7.38 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 25.45, 25.75, 29.00, 35.00, and 66.38 (Ccyclopentane); 41.03 (Me), 41.19 (Me), and 67.65 (CH); 113.65, 117.82, 127.33, 127.98, 135.80, and 137.21 (CAr); 172.14 (CO). Anal. Calc. for C42H46N4O2: C, 78.96; H, 7.26; and N, 8.77. Found: C, 79.17; H, 7.39; and N, 8.58.
2.2.10. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-phenyl-2-azaspiro[3.5]nonan-1-one) (7a)
Yield: 2.18 g (75%), m.p. 312–314°C. IR (ν, cm−1): 1730 (CO). 1H-NMR (δ, ppm): 1.08–2.15 m [20H, 2 (CH2)5], 4.79 s (2H, 2 CH), 7.28–7.35 m (10H, 2 Ph), 7.37 d, and 7.42 d (8H, biphenyl, J = 8.2 Hz). 13C-NMR (δ, ppm): 21.99, 22.31, 25,11, 27.50, 33.40, and 59.75 (Ccyclohexane); 66.44 (CH); 117.43, 127.02, 127.08, 127.96, 128.42, 135.16, 135.60, and 136.84 (CAr); 171.16 (CO). Anal. Calc. for C40H40N2O2: C, 82.72; H, 6.94; and N, 4.82. Found: C, 82.61; H, 7.08; and N, 4.63.
2.2.11. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(p-tolyl)-2-azaspiro[3.5]nonan-1-one) (7b)
Yield: 2.56 g (84%), m.p. 316–319°C. IR (ν, cm−1): 1732 (CO). 1H-NMR (δ, ppm): 1.02–2.15 m [20H, 2 (CH2)5], 2.35 s (6H, 2 Me), 4.74 s (2H, 2 CH), 7.49 s [8H, 2 (4-MeC6H4)], 7.31 d, and 7.39 d (8H, biphenyl, J = 8.4 Hz). 13C-NMR (δ, ppm): 20.98 (Me); 22.02, 23.31, 25.12, 27.46, 33.36, and 59.63 (Ccyclohexane); 66.32 (CH); 117.44, 126.95, 127.02, 129.12, 132.05, 135.53, 136.88, and 137.71 (CAr); 171.29 (CO). Anal. Calc. for C42H44N2O2: C, 82.86; H, 7.28; and N, 4.60. Found: C, 82.59; H, 7.17; and N, 4.69.
2.2.12. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(4-methoxyphenyl)-2-azaspiro[3.5]nonan-1-one) (7c)
Yield: 2.60 g (81%), m.p. 306–308°C. IR (ν, cm−1): 1729 (CO). 1H-NMR (δ, ppm): 1.00–2.10 m [20H, 2 (CH2)5], 3.80 s (6H, 2 MeO), 4.73 s (2H, 2 CH), 6.89 d, 7.20 d [8H, 2 (4-MeOC6H4), J = 8.4 Hz], 7.32 d, and 7.39 d (8H, biphenyl, J = 8.4 Hz). 13C-NMR (δ, ppm): 22.00, 23.31, 25.12, 27.42, 33.29, and 59.66 (Ccyclohexane); 55.09 (MeO); 66.07 (CH); 113.91, 125.62, 127.04, 128.19, 129.44, 135.54, 136.88, and 159.37 (CAr); 171.30 (CO). Anal. Calc. for C42H44N2O4: C, 78.72; H, 6.92; and N, 4.37. Found: C, 78.86; H, 7.04; and N, 4.22.
2.2.13. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(3,4-dimethoxyphenyl)-2-azaspiro[3.5]nonan-1-one) (7d)
Yield: 2.66 g (76%), m.p. 234–236°C. IR (ν, cm−1): 1729 (CO). 1H-NMR (δ, ppm): 1.02–2.11 m [20H, 2 (CH2)5], 3.78 s (6H, 2 MeO), 3.85 s (6H, 2 MeO), 4.69 s (2H, CH), 6.73 s, 6.82 d, 6.83 d [6H, 2 (3,4-(MeO)2C6H3), J = 8.4 Hz], 7.30 d, and 7.37 d (8H, biphenyl, J = 8.4 Hz). 13C-NMR (δ, ppm): 22.36, 23.58, 25.37, 27.69, 33.59, and 59.96 (Ccyclohexane); 56.02 (MeO); 56.19 (MeO); 66.59 (CH); 111.48, 117.69, 119.89, 127.24, 127.80, 128.97, 135.77, 137.16, 149.12, and 149.30 (CAr); 171.61 (CO). Anal. Calc. for C44H48N2O6: C, 75.40; H, 6.90; and N, 4.00. Found: C, 75.66; H, 7.01; and N, 4.18.
2.2.14. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(benzo[d][1,3]dioxol-5-yl)-2-azaspiro[3.5]nonan-1-one) (7e)
Yield: 2.57 g (77%), m.p. 257–260°C. IR (ν, cm−1): 1729 (CO). 1H-NMR (δ, ppm): 1.09–2.10 m [20H, 2 (CH2)5], 4.68 s (2H, 2 CH), 5.97 s (4H, 2 OCH2O), 6.74 s, 6.76 d, 6.80 d [6H, 2 (3,4-OCH2OC6H3), J = 8.4 Hz], 7.32 d, and 7.41 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 22.40, 23.62, 25.45, 27.71, 33.65, and 60.02 (Ccyclohexane); 66.61 (CH); 101.55 (OCH2O); 107.14, 108.88, 117.78, 120.48, 127.47, 130.17, 136.04, 137.22, 147.75, and 148.40 (CAr); 171.77 (CO). Anal. Calc. for C42H40N2O6: C, 75.43; H, 6.03; and N, 4.19. Found: C, 75.70; H, 5.96; and N, 4.31.
2.2.15. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(4-fluorophenyl)-2-azaspiro [3.5]nonan-1-one) (7f)
Yield: 2.25 g (73%), m.p. 284–286°C. IR (ν, cm−1): 1729 (CO). 1H-NMR (δ, ppm): 1.02–2.12 m [20H, 2 (CH2)5], 4.76 s (2H, 2 CH), 7.03–7.08 m, 7.22–7.27 m [8H, 2 (4-FC6H4)], 7.29 d, and 7.40 d (8H, biphenyl, J = 8.6 Hz). 13C-NMR (δ, ppm): 22.00, 23.29, 25,05, 27.48, 33.31, and 59.79 (Ccyclohexane); 65.76 (CH); 115.41, 115.62, 117.40, 127.12, 127.14, 128.57, 128.65, 135.63, 135.66, 136.68, 161.19, and 163.65 (CAr); 170.97 (CO). 19F-NMR (δ, ppm): −114.76. Anal. Calc. for C40H38F2N2O2: C, 77.90; H, 6.21; and N, 4.54. Found: C, 78.14; H, 6.40; and N, 4.68.
2.2.16. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(4-chlorophenyl)-2-azaspiro [3.5]nonan-1-one) (7g)
Yield: 2.34 g (72%), m.p. 318–320°C. IR (ν, cm−1): 1743 (CO). 1H-NMR (δ, ppm): 1.03–2.13 m [20H, 2 (CH2)5], 4.74 s (2H, 2 CH), 7.22 d, 7.29 d [8H, 2 (4-ClC6H4), J = 8.8 Hz], 7.34 d, and 7.40 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 22.04, 23.30, 25.03, 27.52, 33.34, and 59.92 (Ccyclohexane); 65.76 (CH); 117.36, 127.14, 128.33, 128.74, 133.78, 133.90, 135.67, and 136.62 (CAr); 170.84 (CO). Anal. Calc. for C40H38Cl2N2O2: C, 73.95; H, 5.90; Cl, 10.91; and N, 4.31. Found: C, 74.11; H, 5.79; Cl, 11.13; and N, 4.18.
2.2.17. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(2,4-dichlorophenyl)-2-azaspiro [3.5]nonan-1-one) (7h)
Yield: 3.59 g (82%), m.p. 291–293°C. IR (ν, cm−1): 1742 (CO). 1H-NMR (δ, ppm): 1.08–2.23 m [20H, 2 (CH2)5], 5.12 s (2H, 2 CH), 7.12 d (J = 8.4 Hz), 7.19 dd (J = 8.4 Hz, J = 2.0 Hz), 7.49 d (J = 2.0 Hz) [6H, 2 (2,4-Cl2C6H3)], 7.30 d, and 7.45 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 22.90, 23.54, 25.48, 28.20, 33.63, and 60.71 (Ccyclohexane); 62.61 (CH); 117.59, 127.48, 127.56, 129.38, 129.96, 132.08, 133.90, 134.54, 136.08, and 136.77 (CAr); 171.16 (CO). Anal. Calc. for C40H36Cl4N2O2: C, 66.86; H, 5.05; Cl, 19.73; and N, 3.90. Found: C, 66.98; H, 4.89; Cl, 19.51; and N, 4.02.
2.2.18. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(4-(dimethylamino)phenyl)-2-azaspiro[3.5]nonan-1-one) (7i)
Yield: 2.60 g (78%), m.p. 273–276°C. IR (ν, cm−1): 1729 (CO). 1H-NMR (δ, ppm): 1.10–2.04 m [20H, 2 (CH2)5], 2.95 s (12H, 2 Me2N), 4.69 s, (2H, 2 CH), 6.69 d, 7.13 d [8H, 2 (4-Me2NC6H4), J = 8.8 Hz], 7.33 d, and 7.38 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 22.35, 23.64, 25.51, 27.74, 33.59, and 59.90 (Ccyclohexane); 40.52 (Me), 66.67 (CH); 112.38, 117.82, 122.56, 127.29, 128.24, 135.76, and 137.37, 150.44 (CAr); 171.93 (CO). Anal. Calc. for C44H50N4O2: C, 79.24; H, 7.56; and N, 8.40. Found: C, 79.48; H, 7.42; and N, 8.29.
2.2.19. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(3-bromophenyl)-2-azaspiro [3.5]nonan-1-one) (7j)
Yield: 2.55 g (69%), m.p. 340–341°C. IR (ν, cm−1): 1745 (CO). 1H-NMR (δ, ppm): 1.08–2.13 m [20H, 2 (CH2)5], 4.70 s (2H, 2 CH), 7.38 s, 7.42 t, 7.49 d, 7.46 d [8H, 2 (3-BrC6H4), J = 7.2 Hz], 7.29 d, and 7.42 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 22.42, 23.62, 25.36, 27.93, 33.72, and 60.37 (Ccyclohexane); 66.04 (CH); 117.66, 123.01, 125.85, 127.51, 130.29, 130.36, 131.54, 136.04, 136.91, and 138.10 (CAr); 171.10 (CO). Anal. Calc. for C40H38Br2N2O2: C, 65.05; H, 5.19; Br, 21.64; and N, 3.79. Found: C, 65.22; H, 5.02; Br, 21.32; and N, 3.66.
2.2.20. 2,2′-([1,1′-Biphenyl]-4,4′-diyl)bis(3-(4-bromophenyl)-2-azaspiro [3.5]nonan-1-one) (7k)
Yield: 2.81 g (76%), m.p. 322–325°C. IR (ν, cm−1): 1744 (CO). 1H-NMR (δ, ppm): 1.05–2.11 m [20H, 2 (CH2)5], 4.72 s (2H, 2 CH), 7.15 d, 7.28 d [8H, 2 (4-BrC6H4), J = 8.4 Hz], 7.40 d, and 7.49 d (8H, biphenyl, J = 8.8 Hz). 13C-NMR (δ, ppm): 22.38, 23.63, 25.36, 27.87, 33.67, and 60.22 (Ccyclohexane); 66.15 (CH); 117.69, 122.30, 127.48, 128.98, 132.02, 134.65, 136.01, and 136.93 (CAr); 171.16 (CO). Anal. Calc. for C40H38Br2N2O2: C, 65.05; H, 5.19; Br, 21.64; and N, 3.79. Found: C, 65.30; H, 5.24; Br, 21.41; and N, 3.88.