3.6. Synthetic Procedures: Method C
A solution of 1-amino-2-indanol (1.0 mmol) in ethanol was added to a solution of the corresponding salicylaldehyde (2.0 mmol) in ethanol. The mixture was stirred at room temperature for 24 h. Then, it was stored at 5 °C for one week, evaporated to dryness, and the resulting oil crystallized from diethyl ether.
(1R,2S)-1-[(2-Hydroxy-5-methoxybenzylidene)amino]-2-indanol (24). Following procedure A and from 5-methoxysalicylaldehyde, compound 24 was obtained (75%); m.p. 103–105 °C; [α]D20 − 16.4°; [α]57820 − 14.5°; [α]54620 − 4.2° (c 0.5, DMSO); IR (KBr) max/cm−1 3362 (OH), 1647 (C=N), 1623, 1588 (C=C), 1531, 1490 (arom); Raman max/cm−1 1639 (C=N), 1619 (C=C); 1H NMR (500 MHz, DMSO-d6) δ 13.05 (s, 1H, OH), 8.67 (s, 1H, CH=N), 7.31 (d, J = 7.5 Hz, 1H, H-arom), 7.26 (dt, J = 1.5 Hz, J = 8.0 Hz, 1H, H-arom), 7.24 (m, 2H, H-arom), 7.10 (d, J = 3.5 Hz, 1H, H-arom), 6.95 (dd, J = 3.0 Hz, J = 9.0 Hz, 1H, H-arom), 6.79 (d, J = 9 Hz, 1H, H-arom), 5.18 (d, J2,OH = 5.0 Hz, 1H, C2-OH), 4.74 (d, J1,2 = 5.5 Hz, 1H, H-1), 4.54 (q, J = 6.0 Hz, 1H, H-2), 3.73 (s, 3H, CH3), 3.10 (dd, J2,3 = 6.5 Hz, J3,3′ = 15.5 Hz, 1H, H-3), 2.93 (dd, J2,3′ = 6.0 Hz, J3,3′ = 15.5 Hz, 1H, H-3′); 13C NMR (125 MHz, DMSO-d6) δ 165.19 (CH=N), 154.62 (C-OH), 151.15, 141.82, 140.89, 127.76, 126.39, 124.85, 124.43, 119.11, 118.35, 116.99, 114.65 (C-arom), 74.06, 73.83 (C1, C2), 55.30 (CH3), 39.54 (C3). Anal. Calculated for C17H17NO3: C, 72.07; H, 6.05; N, 4.94. Found: C, 71.87; H, 6.15; N, 4.82.
(1R,2S)-1-[(5-Bromo-2-hydroxybenzylidene)amino]-2-indanol (25). Using procedure A and from 5-bromosalicylaldehyde: (51%); m.p. 148–150 °C; [α]D22 − 20.8°; [α]57822 − 18.1°; [α]54622 − 5.6° (c 0.5, DMSO); IR (KBr) max/cm−1 3330 (OH), 1648 (C=N), 1627, 1605 (C=C), 1514, 1499, 1477 (arom); Raman max/cm−1 1638 (C=N), 1625 (C=C); 1H NMR (500 MHz, DMSO-d6) δ 13.92 (bs, 1H, OH), 8.68 (s, 1H, CH=N), 7.70 (d, J = 3.0 Hz, 1H, H-arom), 7.44 (dd, J = 2.5 Hz, J = 8.5 Hz, 1H, H-arom), 7.31 (d, J = 7.0 Hz, 1H, H-arom), 7.26 (dt, J =1.5 Hz, J = 6.5 Hz, 1H, H-arom), 7.19 (m, 2H, H-arom), 6.79 (d, J = 8.5 Hz, 1H, H-arom), 5.28 (d, J2,OH = 5.0 Hz, 1H, C2-OH), 4.79 (d, J1,2 = 5.5 Hz, 1H, H-1), 4.55 (q, J = 5.5 Hz, 1H, H-2), 3.11 (dd, J2,3 = 6.0 Hz, J3,3′ = 16.0 Hz, 1H, H-3), 2.91 (dd, J2,3′ = 6.0 Hz, J3,3′ = 15.5 Hz, 1H, H-3′); 13C NMR (125 MHz, DMSO-d6) δ 164.54 (CH=N), 161.26 (C-OH), 141.48, 141.06, 134.83, 133.61, 128.05, 126.60, 125.05, 124.58, 120.13, 119.39, 108.32 (C-arom), 73.79, 73.47 (C1, C2), 39.02 (C3). Anal. Calculated for C16H14BrNO2: C, 57.85; H, 4.25; N, 4.22. Found: C, 57.66; H, 4.27; N, 4.11.
(1S,2R)-1-[(2-Hydroxy-5-methoxybenzylidene)amino]-2-indanol (31). Using procedure A and from 5-methoxysalicylaldehyde: (59%); m.p. 100–102 °C; [α]D22 + 13.1°; [α]57822 + 11.3°; [α]54622 + 1.4° (c 0.5, DMSO); IR (KBr) max/cm−1 3332 (OH), 1645 (C=N), 1624, 1588 (C=C), 1523, 1492, 1475 (arom); Raman max/cm−1 1639 (C=N), 1619 (C=C); 1H NMR (500 MHz, DMSO-d6) δ 13.05 (s, 1H, OH), 8.67 (s, 1H, CH=N), 7.31 (d, J = 7.5 Hz, 1H, H-arom), 7.26 (dt, J = 1.5 Hz, J = 7.0 Hz, 1H, H-arom), 7.24 (m, 2H, H-arom), 7.10 (d, J = 3.0 Hz, 1H, H-arom), 6.95 (dd, J = 3.5 Hz, J = 9.0 Hz, 1H, H-arom), 6.78 (d, J = 9.0 Hz, 1H, H-arom), 5.18 (d, J2,OH = 5.0 Hz, 1H, C2-OH), 4.74 (d, J1,2 = 5.0 Hz, 1H, H-1), 4.54 (q, J = 5.5 Hz, 1H, H-2), 3.73 (3H, s, CH3), 3.10 (dd, J2,3 = 6.0 Hz, J3,3′ = 15.5 Hz, 1H, H-3), 2.93 (dd, J2,3′ = 6.0 Hz, J3,3′ = 15.5 Hz, 1H, H-3′); 13C NMR (125 MHz, DMSO-d6) δ 165.53 (CH=N), 154.95 (C-OH), 151.48, 142.15, 141.23, 128.09, 126.73, 125.18, 124.76, 119.44, 118.68, 117.32, 114.98 (C-arom), 74.39, 73.17 (C1, C2), 55.63 (CH3) 39.19 (C3); 1H NMR (500 MHz, CDCl3) δ 12.42 (sa, 1H, OH), 8.55 (s, 1H, CH=N), 7.30 (m, 2H, H-arom), 7.23 (dt, J = 1.5 Hz, J = 7.5 Hz, 1H, H-arom), 7.24 (d, J = 7.0 Hz, 1H, H-arom), 6.95 (dd, J = 3.5 Hz, J = 9.0 Hz, 1H, H-arom), 6.89 (d, J = 9.0 Hz, 1H, H-arom), 6.84 (d, J = 3.0 Hz, 1H, H-arom), 4.80 (d, J1,2 = 5.5 Hz, 1H, H-1), 4.69 (c, J = 5.5 Hz, 1H, H-2), 3.79 (s, 3H, CH3), 3.24 (dd, J2,3 = 6.0 Hz, J3,3′ = 16.0 Hz, 1H, H-3), 3.09 (dd, J2,3′ = 5.5 Hz, J3,3′ = 16.0 Hz, 1H, H-3′); 13C NMR (125 MHz, CDCl3) δ 166.60 (CH=N), 155.13 (C-OH), 152.15, 140.71, 140.65, 128.62, 127.06, 125.48, 124.84, 120.06, 118.29, 117.91, 115.13 (C-arom), 75.66, 75.27 (C1, C2), 55.94 (CH3), 39.60 (C3).
(1S,2R)-1-[(5-Bromo-2-hydroxybenzylidene)amino]-2-indanol (32). Using procedure A and from 5-bromosalicylaldehyde: (59%); m.p. 147–149 °C; [α]D25 + 17.2°; [α]57825 + 14.4°; [α]54625 + 2.8° (c 0.5, DMSO); IR (KBr) max/cm−1 3329 (OH), 1648 (C=N), 1627, 1605 (C=C), 1515, 1477 (arom); Raman max/cm−1 1638 (C=N), 1625 (C=C); 1H NMR (500 MHz, DMSO-d6) δ 13.91 (1H, s, OH), 8.69 (s, 1H, CH=N), 7.72 (d, J = 2.5 Hz, 1H, H-arom), 7.44 (dd, J = 2.5 Hz, J = 9.0 Hz, 1H, H-arom), 7.31 (d, J = 7.5 Hz, 1H, H-arom), 7.26 (dt, J = 2.0 Hz, J = 8.5 Hz, 1H, H-arom), 7.19 (m, 2H, H-arom), 6.79 (d, J = 9.0 Hz, 1H, H-arom), 5.24 (d, J2,OH = 5.0 Hz, 1H, C2-OH), 4.79 (d, J1,2 = 5.5 Hz, 1H, H-1), 4.55 (q, J = 5.5 Hz, 1H, H-2), 3.11 (dd, J2,3 = 6.0 Hz, J3,3′ = 15.5 Hz, 1H, H-3), 2.91 (dd, J2,3′ = 5.5 Hz, J3,3′ = 15.5 Hz, 1H, H-3′); 13C NMR (125 MHz, DMSO-d6) δ 164.06 (CH=N), 160.77 (C-OH), 140.98, 140.57, 134.34, 133.09, 127.56, 126.11, 124.56, 124.09, 119.64, 118.91, 107.83 (C-arom), 73.29, 72.97 (C1, C2), 38.52 (C3). Anal. Calculated for C16H14BrNO2: C, 57.85; H, 4.25; N, 4.22. Found: C, 57.56; H, 4.31; N, 3.93.
(1R,2R)-1-[(3,5-Di-tert-butyl-2-hydroxybenzylidene)amino]-2-indanol (37). Using procedure A and from 3,5-di-tert-butylsalicylaldehyde: (78%); m.p. 69–71 °C; [α]D25 − 48.5°; [α]57825 − 49.5°; [α]54625 + 50.9° (c 0.5, DMSO); IR (KBr) max/cm−1 3339 (OH), 1627 (C=N), 1596, 1475 (arom); Raman max/cm−1 1622 (C=N), 1591 (C=C); 1H NMR (500 MHz, DMSO-d6) δ 13.96 (s, 1H, OH), 8.75 (s, 1H, CH=N), 7.39 (d, J = 2.0 Hz, 1H, H-arom),7.34 (s, 1H, H-arom), 7.23 (m, 3H, H-arom), 7.08 (d, J = 7.5 Hz, 1H, H-arom), 5.53 (d, J2,OH = 5.5 Hz, 1H, C2-OH), 4.63 (d, J1,2 = 6.0 Hz, 1H, H-1), 4.39 (q, J1,2 = J2,3 = J2,OH = 6.5 Hz, 1H, H-2), 3.23 (dd, J2,3 = 7.0 Hz, J3,3′ = 15.5 Hz, 1H, H-3), 2.84 (dd, J2,3′ = 8.0 Hz, J3,3′ = 15.5 Hz, 1H, H-3′), 1.37 (s, 9H, CH3), 1.29 (s, 9H, CH3); 13C NMR (125 MHz, DMSO-d6) δ 167.79 (CH=N), 157.37 (C-OH), 141.50, 139.66, 139.53, 135.45, 127.85, 126.72, 126.52, 126.14, 124.68, 123.78, 117.78 (C-arom), 79.17, 78.94 (C1,C2), 38.92 (C3), 34.43, 33.76 (C-(CH3)3), 31.19, 29.14 (CH3). Anal. Calculated for C28H33NO3: C, 76.62; H, 8.12; N, 3.44. Found: C, 76.31; H, 7.95; N, 3.33.
(6Z)-6-[(1R,2S)-(2-hydroxyindan-1-yl)amino]methylen]-4-nitrocyclohexa-2,4-dienone (38). Using procedure A and from 5-nitrosalicylaldehyde, compound 38 was obtained: (91%); m.p. 212–214 °C; [α]D20 + 35.2°; [α]57820 + 40.9°; [α]54620 + 63.9° (c 0.5, DMSO); IR (KBr) max/cm−1 3174 (OH), 1655 (C=O), 1611 (C=C), 1544 (NO2), 1515, 1441 (arom), 1330 (NO2); Raman max/cm−1 1655 (C=O), 1603 (C=C); 1H NMR (500 MHz, DMSO-d6) δ 14.49 (bs, 1H, NH), 8.94 (s, 1H, CH-N), 8.53 (d, J =3.0 Hz, 1H, H-cyclo), 8.04 (dd, J = 3.0 Hz, J =9.5 Hz, 1H, H-cyclo), 7.33 (m, 3H, H-arom), 7.27 (m, 1H, H-arom), 6.58 (d, J = 9.5 Hz, 1H, H-cyclo), 5.74 (d, J2,OH = 2.5 Hz, 1H, C2-OH), 5.20 (d, J1,2 = 4.5 Hz, 1H, H-1), 4.65 (bs, 1H, H-2), 3.18 (dd, J2,3 = 5.5 Hz, J3,3′ = 16.0 Hz, 1H, H-3), 2.91 (dd, J2,3′ = 2.5 Hz, J3,3′ = 16.0 Hz, 1H, H-3′); 13C NMR (125 MHz, DMSO-d6) δ 178.06 (C=O), 166.86 (C-NH), 140.99, 138.77, 133.45, 132.74, 129.12, 128.55, 126.70, 125.19, 124.36, 122.75, 113.30 (C-arom), 72.04, 68.09 (C1, C2), 39.93 (C3). Anal. Calculated for C18H14N2O4: C, 64.42; H, 4.73; N, 9.39. Found: C, 64.66; H, 4.81; N, 9.64.
(6Z)-6-[(1R,2S)-(2-hydroxyindan-1-yl)amino]methylen]-5-bromocyclohexa-2,4-dienone (39). Using procedure A and from 5-bromosalicylaldehyde: (62%); m.p. 179–181 °C; [α]D20 + 109.01°; [α]57820 + 121.10°; [α]54620 + 170.11° (c 0.5, DMSO); IR (KBr) max/cm−1 3174 (OH), 1642 (C=N), 1597, 1502, 1454 (arom); Raman max/cm−1 1641 (C=N);1H NMR (500 MHz, DMSO-d6) δ 14.32 (bs, 1H, OH), 8.69 (s, 1H, CH=N), 7.39 (d, J = 8.0 Hz, 1H, H-arom), 7.32 (d, J = 7.0 Hz, 1H, H-arom), 7.28 (m, 1H, H-arom), 7.21 (m, 2H, H-arom), 6.97 (d, J = 1.5 Hz, 1H, H-arom), 6.92 (dd, J = 2.0 Hz, J = 8.5 Hz, 1H, H-arom), 5.33 (d, J2,OH = 5.0 Hz, 1H, C2-OH), 4.87 (d, J1,2 = 5.0 Hz, 1H, H-1), 4.56 (q, J = 5.5 Hz, 1H, H-2), 3.12 (dd, J2,3 = 6.0 Hz, J3,3′ = 16.0 Hz, 1H, H-3), 2.91 (dd, J2,3′ = 5.0 Hz, J3,3′ = 15.5 Hz, 1H, H-3′); 13C NMR (125 MHz, DMSO-d6) δ 165.89 (C-OH), 165.23 (CH=N), 141.03, 133.75, 128.15, 126.64, 125.11, 124.53, 120.88, 119.60, 116.78 (C-arom), 73.39, 71.99 (C1, C2), 39.09 (C3). Anal. Calculated for C16H14BrNO2: C, 57.85; H, 4.25; N, 4.22. Found: C, 57.73; H, 4.29; N, 4.19.
(6Z)-6-[(1R,2S)-(2-hydroxyindan-1-yl)amino]methylen]-5-methoxycyclohexa-2,4-dienone(40). Using procedure A and from 4-methoxysalicylaldehyde: (86%); m.p. 169–171 °C; [α]D22 + 157.9°; [α]57822 + 172.5°; [α]54622 + 228.4° (c 0.5, DMSO); IR (KBr) max/cm−1 3182 (OH), 1644 (C=O), 1616 (C=C), 1514, 1484 (arom); Raman max/cm−1 1638 (C=O), 1608 (C=C); 1H NMR (500 MHz, DMSO-d6) δ 14.01 (s, 1H, OH), 8.49 (s, 1H, CH=N), 7.31 (d, J = 7.5 Hz, 1H, H-cyclo), 7.26 (m, 2H, H-arom), 7.21 (m, 2H, H-arom), 6.30 (dd, J = 2.5 Hz, J = 8.5 Hz, 1H, H-cyclo), 6.20 (d, J = 2.5 Hz, 1H, H-cyclo), 5.30 (d, J2,OH = 4.5 Hz, 1H, C2-OH), 4.81 (d, J1,2 = 5.5 Hz, 1H, H-1), 4.54 (q, J = 4.5 Hz, 1H, H-2), 3.74 (s, 3H, CH3), 3.11 (dd, J2,3 = 6.0 Hz, J3,3′ = 16.0 Hz, 1H, H-3), 2.90 (dd, J2,3′ = 4.5 Hz, J3,3′ = 15.5 Hz, 1H, H-3′); 13C NMR (125 MHz, DMSO-d6) δ 168.92 (C-OH), 164.03 (CH=N), 163.93, 141.48, 140.94, 133.56, 127.99, 126.59, 125.07, 124.40, 111.68, 105.49, 101.24 (C-arom), 73.33, 71.26 (C1, C2), 55.07 (CH3) 39.35 (C3). Anal. Calculated for C17H17NO3: C, 72.07; H, 6.05; N, 4.94. Found: C, 71.83; H, 6.05; N, 4.91.
(6Z)-6-[(1R,2S)-(2-hydroxyindan-1-yl)amino]methylen]-4,6-dinitrocyclohexa-2,4-dienone(41). Using procedure A and from 3,5-dinitrosalicylaldehyde: (80%); m.p. 145–147 °C; [α]D25 + 211.5°; [α]57825 + 234.34°; [α]54625 + 334.9°; (c 0.5, DMSO); IR (KBr) max/cm−1 3407, 3350 (OH), 1650 (C=O), 1616 (C=C), 1556 (NO2) 1531 (arom); Raman max/cm−1 1666 (C=O); 1H NMR (500 MHz, DMSO-d6) δ 13.86 (bs, 1H, NH), 9.10 (d, J = 14.0 Hz, 1H, CH-N), 8.82 (d, J = 2.5 Hz, 1H, H-cyclo), 8.76 (d, J = 3.0 Hz, 1H, H-cyclo), 7.36 (m, 3H, H-arom), 7.28 (dt, J = 2.5 Hz, J = 6.5 Hz, 1H, H-arom), 5.94 (d, J2,OH = 4.5 Hz, 1H, C2-OH), 4.37 (t, J1,2 = JNH,1 = 7.0 Hz, 1H, H-1), 4.70 (m, 1H, H-2), 3.22 (dd, J2,3 = 5.5 Hz, J3,3′ = 16.5 Hz, 1H, H-3), 2.94 (dd, J2,3′ = 5.0 Hz, J3,3′ = 16.5 Hz, 1H, H-3′); 13C NMR (125 MHz, DMSO-d6) δ 169.99 (C=O), 167.97 (CH-N), 141.36,140.83, 137.67, 137.31, 129.88, 129.04, 127.00, 126.96, 125.46, 124.70, 117.06 (C-arom), 71.79, 67.51 (C1, C2), 39.68 (C3). Anal. Calculated for C16H13N3O6: C, 55.98; H, 3.82; N, 12.24. Found: C, 55.98; H, 3.85; N, 12.25.
(6Z)-6-[(1R,2S)-(2-hydroxyindan-1-yl)amino]methylen]cyclohexa-2,4-dienone(42). Using procedure B and from salicylaldehyde: (28%); m.p. 113–115 °C; [α]D22 + 16.3°; [α]57822 + 19.4°; [α]54622 + 36.3 (c 0.5, DMSO); IR (KBr) max/cm−1 3015 (OH), 1634 (C=O), 1607 (C=C), 1513, 1473 (arom); Raman max/cm−1 1635 (C=O); 1H NMR (500 MHz, DMSO-d6) δ 13.73 (s, 1H, OH), 8.71 (s, 1H, CH=N), 7.50 (dd, J = 2.0 Hz, J = 8.0 Hz, 1H, H-arom), 7.33 (dd, J = 2.0 Hz, J = 8.5 Hz, 2H, H-arom), 7.27 (m, 1H, H-arom), 7.20 (m, 2H, H-arom), 6.87 (dt, J = 1.5 Hz, J = 7.5 Hz, 1H, H-arom), 6.84 (d, J = 8.0 Hz, 1H, H-arom), 5.19 (d, J2,OH = 5.5 Hz, 1H, C2-OH), 4.78 (d, J1,2 = 5.5 Hz, 1H, H-1), 4.56 (q, J = 6.0 Hz, 1H, H-2), 3.13 (dd, J2,3 = 6.0 Hz, J3,3′ = 15.5 Hz, 1H, H-3), 2.94 (dd, J2,3′ = 6.0 Hz, J3,3′ = 15.5 Hz, 1H, H-3′); 13C NMR (125 MHz, DMSO-d6) δ 166.24 (CH=N), 161.80 (C-OH), 142.48, 141.60, 132.81, 132.28, 128.50, 127.12, 125.58, 125.15, 119.26, 118.64, 117.14 (C-arom), 74.50, 74, 45 (C1,C2), 39.85 (C3); 1H NMR (500 MHz, CD3OD) δ 8.61 (s, 1H, CH=N), 7.38 (dd, J = 1.5 Hz, J = 3.0 Hz, 1H, H-arom), 7.31 (m, 3H, H-arom), 7.21 (m, 2H, H-arom), 6.82 (m, 2H, H-arom), 4.85 (d, J1,2 = 5.0 Hz, 1H, H-1), 4.64 (q, J1,2 = J2,3 = 5.5 Hz, 1H, H-2), 3.21 (dd, J2,3 = 6.0 Hz, J3,3′ = 16 Hz, 1H, H-3), 3.06 (dd, J2,3′ = 5.0 Hz, J3,3′ = 15.5 Hz, 1H, H-3′); 13C NMR (125 MHz, CD3OD) δ 167.33 (CH=N), 162.49 (C-OH), 142.22, 142.10, 134.53, 129.56, 128.05, 126.33, 125.74, 122.62, 120.91, 119.04, 118.75 (C-arom), 75.76, 74.76 (C1,C2), 40.09 (C3). Anal. Calculated for C16H15NO2: C, 75.87; H, 5.97; N, 5.53. Found: C, 75.98; H, 5.98; N, 5.71.
(6Z)-6-[(1S,2R)-(2-hydroxyindan-1-yl)amino]methylen]-4-nitrocyclohexa-2,4-dienone(43). Using procedure A and from 5-nitrosalicylaldehyde, compound 43 was obtained: (85%); m.p. 219–221 °C; [α]D22 − 45.5°; [α]57822 − 52.5°; [α]54622 − 80.4°; [α]43622 43.7° (c 0.5, DMSO); IR (KBr) max/cm−1 3209 (OH), 1656 (C=O), 1610 (arom), 1543 (NO2), 1514, 1444 (arom), 1330 (NO2); Raman max/cm−1 1655 (C=O), 1603 (C=C); 1H NMR (500 MHz, DMSO-d6) δ 14.50 (bs, 1H, NH), 8.95 (s, 1H, CH-N), 8.54 (d, J = 3.0 Hz, 1H, H-cyclo), 8.05 (dd, J = 3.0 Hz, J = 9.5 Hz, 1H, H-cyclo), 7.33 (m, 3H, H-arom), 7.27 (m, 1H, H-arom), 6.59 (d, J = 10.0 Hz, 1H, H-cyclo), 5.75 (d, J2,OH = 3.0 Hz, 1H, C2-OH), 5.20 (d, J1,2 = 5.0 Hz, 1H, H-1), 4.66 (sa, 1H, H-2), 3.19 (dd, J2,3 = 5.5 Hz, J3,3′ = 16.5 Hz, 1H, H-3), 2.91 (dd, J2,3′ = 3.0 Hz, J3,3′ = 16.5 Hz, 1H, H-3′); 13C NMR (125 MHz, DMSO-d6) δ 178.10 (C=O), 166.88 (C-NH), 140.99, 138.78, 133.45, 132.76, 129.14, 128.56, 126.71, 125.20, 124.37, 122.79, 113.30 (C-arom), 72.05, 68.10 (C1, C2), 39.96 (C3).
(6Z)-6-[(1S,2R)-(2-hydroxyindan-1-yl)amino]methylen]-5-methoxycyclohexa-2,4-dienone(44). Using procedure A and from 4-methoxysalicylaldehyde: (88%); m.p. 170–172 °C; [α]D22 − 167.6°; [α]57822 − 182.5°; [α]54622 − 241.1° (c 0.5, DMSO); IR (KBr) max/cm−1 3186 (OH), 1644 (C=O), 1615 (C=C), 1514, 1484, 1456 (arom); Raman max/cm−1 1638 (C=O), 1608 (C=C);1H NMR (500 MHz, DMSO-d6) δ 14.01 (s, 1H, OH), 8.49 (s, 1H, CH=N), 7.31 (d, J = 7.0 Hz, 1H, H-cyclo), 7.26 (m, 2H, H-arom), 7.20 (m, 2H, H-arom), 6.30 (dd, J = 2.0 Hz, J = 8.5 Hz, 1H, H-cyclo), 6.20 (d, J = 2.0 Hz, 1H, H-cyclo), 5.29 (d, J2,OH = 4.0 Hz, 1H, C2-OH), 4.81 (d, J1,2 = 5.0 Hz, 1H, H-1), 4.54 (q, J = 4.0 Hz, 1H, H-2), 3.74 (s, 3H, CH3), 3.10 (dd, J2,3 = 6.0 Hz, J3,3′ = 16.0 Hz, 1H, H-3), 2.89 (dd, J2,3′ = 5.0 Hz, J3,3′ = 16.0 Hz, 1H, H-3′); 13C NMR (125 MHz, DMSO-d6) δ 168.88 (C-OH), 164.03 (CH=N), 163.92, 141.48, 140.94, 133.54, 127.98, 126.58, 125.06, 124.39, 111.68, 105.48, 101.23 (C-arom), 73.32, 71.26 (C1, C2), 55.06 (CH3) 36.68 (C3). Anal. Calculated for C17H17NO3: C, 72.07; H, 6.05; N, 4.94. Found: C, 71.83; H, 6.05; N, 4.91.
(6Z)-6-[(1S,2R)-(2-hydroxyindan-1-yl)amino]methylen]cyclohexa-2,4-dienone(45). Using procedure B and from salicylaldehyde: (35%); m.p. 110–112 °C; [α]D18 − 15.2°; [α]57818 − 17.9°; [α]54618 − 33.6 (c 0.5, DMSO); IR (KBr) max/cm−1 3119 (OH), 1639 (C=O), 1611 (C=C), 1513, 1490 (arom); Raman max/cm−1 1635 (C=O); 1H NMR (500 MHz, DMSO-d6) δ 13.74 (s, 1H, OH), 8.71 (s, 1H, CH=N), 7.49 (dd, J = 1.0 Hz, J = 7.5 Hz, 1H, H-arom), 7.33 (m, 2H, H-arom), 7.27 (m, 1H, H-arom), 7.20 (m, 2H, H-arom), 6.90 (t, J = 7.5 Hz, 1H, H-arom), 6.84 (d, J = 8.0 Hz, 1H, H-arom), 5.21 (d, J2,OH = 5.0 Hz, 1H, C2-OH), 4.78 (d, J1,2 = 5.5 Hz, 1H, H-1), 4.56 (q, J = 5.5 Hz, 1H, H-2), 3.12 (dd, J2,3 = 6.5 Hz, J3,3′ = 16.0 Hz, 1H, H-3), 2.94 (dd, J2,3′ = 5.5 Hz, J3,3′ = 15.5 Hz, 1H, H-3′); 13C NMR (125 MHz, DMSO-d6) δ 165.87 (CH=N), 161.41 (C-OH), 141.22, 132.44, 131.89, 128.12, 126.74, 125.20, 124.77, 118.26, 116.76 (C-arom), 74.11, 74.08 (C1,C2), 39.27 (C3). Anal. Calculated for C16H15NO2: C, 75.87; H, 5.97; N, 5.53. Found: C, 75.47; H, 5.90; N, 5.35.
Reaction of (1R,2S)-1-amino-2-indanol with salicylaldehyde. Using procedure C and from salicylaldehyde, compound 47 was obtained: (88%); m.p. 157–158 °C; [α]D18 + 26.1°; [α]57818 + 27.0°; [α]54618 + 31.7°; [α]43618 + 66.0° (c 0.5, CHCl3); IR (KBr) max/cm−1 3187 (OH), 1619, 1589 (arom), 1253, 1221 (C-O-C), 1027 (C-O); 1H NMR (500 MHz, DMSO-d6) δ 9.91 (s, 1H, OH), 7.81 (dd, J = 1.5 Hz, J = 7.5 Hz, 1H, H-arom), 7.32 (m, 2H, H-arom), 7.27 (m, 1H, H-arom), 7.24 (m, 2H, H-arom), 7.20 (m, 2H, H-arom), 7.05 (dt, J = 1.0 Hz, J = 8.0 Hz, 1H, H-arom), 6.99 (m, 2H, H-arom), 6.93 (d, J = 8.0 Hz, 1H, H-arom), 5.75 (s, 1H, H-2 oxazine), 4.92 (s, 1H, H-2 oxazolidine), 4.83 (dt, J2,3′ = 1.0 Hz, J1,2 = J2,3 = 6.0 Hz, 1H, H-2 indanol), 4.61 (d, J1,2 = 5.5 Hz, 1H, H-1 indanol), 3.23 (dd, J2,3 = 6.5 Hz, J3,3′ = 18.0 Hz, 1H, H-3 indanol), 3.14 (d, J3,3′ = 17.5 Hz, 1H, H-3′ indanol); 13C NMR (125 MHz, DMSO-d6) δ 156.66 (C-OH), 153.85, 142.60, 140.05, 130.94, 130.42, 130.04, 129.57, 128.89, 127.48, 125.73, 125.20, 123.88, 121.72, 120.07, 119.73, 116.57, 116.12 (C-arom), 86.72 (C2 oxazolidine), 81.12 (C2 oxazine), 77.17 (C2 indanol), 70.53 (C1 indanol), 40.17 (C3 indanol); 1H NMR (500 MHz, CD3OD) δ 7.69 (dd, J = 1.5 Hz, J = 7.5 Hz, 1H, H-arom), 7.32 (m, 6H, H-arom), 7.22 (m, 1H, H-arom), 7.24 (m, 2H, H-arom), 7.04 (m, 2H, H-arom), 6.94 (t, J = 8.5 Hz, 2H, H-arom), 5.73 (s, 1H, H-2 oxazine), 5.02 (s, 1H, H-2 oxazolidine), 4.77 (d, J1,2 = J2,3 = 6.0 Hz, 1H, H-2 indanol), 4.62 (s, 1H, H-1 indanol), 3.25 (d, J2,3 = 5.5 Hz, 2H, H-3, H-3′ indanol); 13C NMR (125 MHz, CD3OD) δ 157.76(C-OH), 155.11, 143.55, 140.64, 132.00, 131.26, 130.98, 130.58, 129.83, 128.42, 126.82, 125.85, 124.38, 122.69, 121.07, 120.49, 117.63, 117,08 (C-arom), 87.94 (C2 oxazolidine) 84.73 (C2 oxazine) 78.70 (C2 indanol), 71.97 (C1 indanol), 40.19 (C3 indanol). HRMS-CI (C23H19NO3 [M+H]+): calculated 358.1457; found 358.1443.
Reaction of (1S,2R)-1-amino-2-indanol with salicylaldehyde. Using procedure C and from salicylaldehyde, compound 48 was obtained: (20%); m.p. 152–154 °C; [α]D18 − 23.9°; [α]57818 − 25.2°; [α]54618 − 29.3°; [α]43618 − 61.0° (c 0.5, CHCl3); IR (KBr) max/cm−1 3201 (OH), 1617, 1587 (arom), 1250, 1225 (C-O-C), 1025 (C-O); 1H NMR (500 MHz, DMSO-d6) δ 9.91 (s, 1H, OH), 7.81 (dd, J = 1.5 Hz, J = 8.0 Hz, 1H, H-arom), 7.31 (m, 2H, H-arom), 7.27 (m, 1H, H-arom), 7.23 (m, 2H, H-arom), 7.20 (m, 2H, H-arom), 7.05 (t, J = 7.5 Hz, 1H, H-arom), 6.98 (m, 2H, H-arom), 6.93 (d, J = 8.5 Hz, 1H, H-arom), 5.75 (s, 1H, H-2 oxazine), 4.91 (s, 1H, H-2 oxazolidine), 4.83 (t, J1,2 = J2,3 = 6.0 Hz, 1H, H-2), 4.60 (d, J1,2 = 6.0 Hz, 1H, H-1), 3.22 (dd, J2,3 = 6.0 Hz, J3,3′ = 18.0 Hz, 1H, H-3), 3.13 (d, J3,3′ = 18.0 Hz, 1H, H-3′); 13C NMR (125 MHz, DMSO-d6) δ 156.65 (C-OH), 153.84, 142.60, 140.03, 130.94, 130.42, 130.04, 129.57, 128.89, 127.48, 125.72, 125.20, 123.86, 121.72, 120.07, 119.72, 116.57, 116.10 (C-arom), 86.71 (C2 oxazolidine), 81.10 (C2 oxazine), 77.16 (C2 indanol), 70.53 (C1 indanol), 39.30 (C3 indanol).
3.7. General Acetylation Procedure
For a solution of the corresponding imine (1.0 mmol) in pyridine (3.0 mL), acetic anhydride (2.0 mL) was added. The mixture was kept at room temperature for 24 h and then was poured into ice water. The resulting white solid was filtered and washed with water. The mixture containing imine and oxazolidine was purified by fractional crystallization from ethanol. The first crystalline material corresponds to acetylated imine, while the mother liquors contain the oxazolidine derivative.
(1R,2S)-2-O-Acetyl-1-[(3,5-di-tert-butyl-2-hydroxybenzylidene)amino]-2-indanol(52). Following the above procedure and 35: 45%; m.p. 144–146 °C; [α]D20 − 100.0°; [α]57820 − 103.1°; [α]54620 − 114.2° (c 0.5, CHCl3); IR (KBr) max/cm−1 1739 (C=O), 1627 (C=N), 1594, 1473 (arom); 1H NMR (400 MHz, CDCl3) δ 13.64 (s, 1H, OH), 8.52 (s, 1H, CH=N), 7.41 (d, J = 2.4 Hz, 1H, H-arom), 7.34 (m, 2H, H-arom), 7.27 (m, 1H, H-arom), 7.20 (d, J = 7.6 Hz, 1H, H-arom), 7.15 (d, J = 2.8 Hz, 1H, H-arom), 5.68 (1H, c, J1,2 = J2,3 = J2,3′ 5.6 Hz, H-2), 5.04 (d, J1,2 = 6.0 Hz, 1H, H-1), 3.35 (dd, J2,3 = 6.8 Hz, J3,3′ = 16.4 Hz, 1H, H-3), 2.28 (dd, J2,3′ = 5.2 Hz, J3,3′ = 16.4 Hz, 1H, H-3′), 2.07 (s, 3H, OCH3), 1.44 (s, 9H, CH3), 1.34 (s, 9H, CH3); 13C NMR (100 MHz, CDCl3) δ 171.01 (C=O), 167.00 (CH=N), 158.28 (C-OH), 140.79, 140.04, 139.85, 136.76, 128.66, 127.35,127.30, 126.27,125.07, 124.95, 117.79 (C-arom), 76.06, 73.17 (C1, C2), 36.84 (C3), 35.05, 34.16 (C-(CH3)3), 31.52, 29.38 (CH3), 20.97 (OCH3). 1H NMR (400 MHz, DMSO-d6) δ 14.13 (s, 1H, OH), 8.79 (s, 1H, CH=N), 7.36 (m, 4H, H-arom), 7.25 (t, J = 6.4 Hz, 1H, H-arom), 7.18 (d, J = 7.2 Hz, 1H, H-arom), 5.64 (sa, 1H, H-2), 5.10 (d, J1,2 = 4.8 Hz, 1H, H-1), 3.36 (m, 1H, H-3), 3.11 (dd, J2,3′ = 2.4 Hz, J3,3′ = 16.8 Hz, 1H, H-3′), 1.95 (s, 3H, OCH3), 1.36 (s, 9H, CH3), 1.29 (s, 9H, CH3); 13C NMR (100 MHz, DMSO-d6) δ 170.29 (C=O), 168.99 (CH=N), 158.35 (C-OH), 141.56, 140.37, 140.11, 136.18, 128.82, 127.57, 127.11, 127.08, 125.42, 124.89, 118.20 (C-arom), 76.39, 72.59 (C1,C2), 37.11 (C3), 35.04, 34.34 (C-(CH3)3), 31.76, 29.68 (CH3), 21.05 (OCH3). Anal. Calculated for C26H33NO3: C, 76.62; H, 8.16; N, 3.44. Found: C, 76.35; H, 8.07; N, 3.35.
N-Acetyl-3,5-di-tert-butyl-2-{(2R,3aR,8aS)-3,3a,8,8a-tetrahydro-2H-indeno [1,2-d]oxazol-2-yl}phenol(53). Following the general procedure from compound 35: 11%; m.p. 164–166 °C; [α]D20 − 208.8°; [α]57820 − 217.8°; [α]54620 − 250.3°; [α]43620 − 449.7° (c 0.5, CHCl3); IR (KBr) max/cm−1 3118 (OH), 1622 (C=O), 1602, 1480 (arom); 1H NMR (400 MHz, CDCl3) δ 9.15 (s, 1H, OH), 7.46 (d, J = 7.6 Hz, 1H, H-arom), 7.40 (t, J = 7.2 Hz, 1H, H-arom), 7.33 (d, J = 7.6 Hz, 1H, H-arom), 7.27 (m, 1H, H-arom), 7.16 (d, J = 2.4 Hz, 1H, H-arom), 6.63 (s, 1H, CH), 6.23 (d, J = 2.4 Hz, 1H, H-arom), 5.50 (d, J1,2 = 4.8 Hz, 1H, H-1), 5.06 (t, J1,2 = J2,3′ = 4.4 Hz, 1H, H-2), 3.43 (d, J3,3′ = 17.2 Hz, 1H, H-3), 3.28 (dd, J2,3′ = 4.4 Hz, J3,3′ = 17.2 Hz, 1H, H-3′), 2.44 (s, 3H, OCH3), 1.41 (s, 9H, CH3), 0.91 (s, 9H, CH3); 13C NMR (100 MHz, CDCl3) δ 170.14 (C=O), 151.95 (C-OH), 141.66, 141.17, 139.91, 138.03, 129.36, 127.77, 126.05, 125.26, 124.93, 124.46, 121.25 (C-arom), 86.57 (CH) 82.34 (C2), 66.61 (C1), 37.09 (C3), 35.04, 33.97 (C-(CH3)3), 31.20, 29.82 (CH3), 23.22 (OCH3). Anal. Calculated for C26H33NO3: C, 76.62; H, 8.16; N, 3.44. Found: C, 76.37; H, 8.08; N, 3.45.
(1S,2R)-2-O-Acetyl-1-[(3,5-di-tert-butyl-2-hydroxybenzylidene)amino]-2-indanol(54). Following the general procedure from compound 36: 44%; m.p. 145–147 °C; [α]D20 + 115.2°; [α]57820 + 117.9°; [α]54620 + 132.4° (c 0.5, CHCl3); IR (KBr) max/cm−1 1739 (C=O), 1627 (C=N), 1595, 1473 (arom); 1H NMR (400 MHz, CDCl3) δ 13.62 (s, 1H, OH), 8.51 (s, 1H, CH=N), 7.42 (d, J = 2.4 Hz, 1H, H-arom), 7.34 (m, 2H, H-arom), 7.28 (m, 1H, H-arom), 7.21 (d, J = 7.2 Hz, 1H, H-arom), 7.16 (d, J = 2.4 Hz, 1H, H-arom), 5.69 (c, J1,2 = J2,3 = J2,3′ = 5.6 Hz, 1H, H-2), 5.04 (d, J1,2 = 6.0 Hz, 1H, H-1), 3.36 (dd, J2,3 = 6.4 Hz, J3,3′ = 16.4 Hz, 1H, H-3), 2.28 (dd, J2,3′ = 5.2 Hz, J3,3′ = 16.4 Hz, 1H, H-3′), 2.06 (s, 3H, OCH3), 1.44 (s, 9H, CH3), 1.35 (s, 9H, CH3); 13C NMR (100 MHz, CDCl3) δ 170.97 (C=O), 166.98 (CH=N), 158.29 (C-OH), 140.79, 140.05, 139.85, 136.77, 128.66, 127.34, 127.30, 126.26, 125.06, 124.95, 117.81 (C-arom), 76.05, 73.15 (C1, C2), 36.83 (C3), 35.05, 34.16 (C-(CH3)3), 31.51, 29.39 (CH3), 20.94 (OCH3). Anal. Calculated for C26H33NO3: C, 76.62; H, 8.16; N, 3.44. Found: C, 76.39; H, 8.09; N, 3.34.
N-Acetyl-3,5-di-tert-butyl-2-{(2S,3aS,8aR)-3,3a,8,8a-tetrahydro-2H-indeno [1,2-d]oxazol-2-yl}phenol(55). Following the general procedure from compound 36: 10%; m.p. 166–168 °C; [α]D20 + 242.8°; [α]57820 + 255.1°; [α]54620 + 292.2°; [α]43620 + 523.5° (c 0.5, CHCl3); IR (KBr) max/cm−1 3117 (OH), 1623 (C=O), 1602, 1480 (arom); 1H NMR (500 MHz, CDCl3) δ 9.15 (s, 1H, OH), 7.46 (d, J = 7.5 Hz, 1H, H-arom), 7.40 (t, J = 7.0 Hz, 1H, H-arom), 7.33 (d, J = 7.5 Hz, 1H, H-arom), 7.27 (m, 1H, H-arom), 7.16 (d, J = 2.0 Hz, 1H, H-arom), 6.63 (s, 1H, CH), 6.22 (d, J = 2.0 Hz, 1H, H-arom), 5.50 (d, J1,2 = 4.5 Hz, 1H, H-1), 5.07 (t, J1,2 = J2,3′ = 4.5 Hz, 1H, H-2), 3.43 (d, J3,3′ =17.5 Hz, 1H, H-3), 3.29 (dd, J2,3′ = 4.0 Hz, J3,3′ = 17.5 Hz, 1H, H-3′), 2.45 (s, 3H, OCH3), 1.41 (s, 9H, CH3), 0.91 (s, 9H, CH3); 13C NMR (125 MHz, CDCl3) δ 170.26 (C=O), 151.96 (C-OH), 141.65, 141.17, 139.92, 138.03, 129.35, 127.77, 126.04, 125.26, 124.93, 124.44, 121.26 (C-arom), 86.59 (CH) 82.34 (C2), 66.63 (C1), 37.10 (C3), 35.04, 33.97 (C-(CH3)3), 31.21, 29.83 (CH3), 23.21 (OCH3).
(1R,2R)-2-O-Acetyl-1-[(3,5-di-tert-butyl-2-hydroxybenzylidene)amino]-2-indanol(56). Following the general procedure from compound 37: 64%; m.p. 106–108 °C; [α]D25 − 48.1°; [α]57825 − 48.5°; [α]54625 − 51.3°; [α]43625 − 28.7° (c 0.5, CHCl3); IR (KBr) max/cm−1 1737 (C=O), 1625 (C=N), 1598, 1460 (arom); 1H NMR (500 MHz, CDCl3) δ 13.25 (sa, 1H, OH), 8.55 (s, 1H, CH=N), 7.42 (d, J = 2.0 Hz, 1H, H-arom), 7.27 (m, 3H, H-arom), 7.16 (m, 2H, H-arom), 5.45 (c, J1,2 = J2,3 = J2,3′ = 6.0 Hz, 1H, H-2), 4.88 (d, J1,2 = 5.5 Hz, 1H, H-1), 3.63 (dd, J2,3 = 7.0 Hz, J3,3′ = 16.0 Hz, 1H, H-3), 2.93 (dd, J2,3′ = 6.0 Hz, J3,3′ = 16.5 Hz, 1H, H-3′), 2.08 (s, 3H, OCH3), 1.44 (s, 9H, CH3), 1.35 (s, 9H, CH3); 13C NMR (125 MHz, CDCl3) δ 170.81 (C=O), 167.31 (CH=N), 158.08 (C-OH), 140.37, 140.29, 139.49, 136.90, 128.67, 127.50, 127.32, 126.32, 125.04, 124.55, 117.68 (C-arom), 81.19, 77.62 (C1, C2), 37.14 (C3), 35.06, 34.19 (C-(CH3)3), 31.52, 29.2 (CH3), 21.17 (OCH3).