The Journal of Organic Chemistry
Article
C16H21NO3: C, 69.79; H, 7.69; N, 5.09. Found: C, 69.72; H, 7.68; N,
5.04.
132.4 (s), 133.6 (s), 167.8 (s). Anal. Calcd for C12H13NO: C, 76.98;
H, 7.00; N, 7.48. Found: C, 76.83; H, 6.95; N, 7.36.
3-(Propan-2-ylidene)isoindolin-1-one (4b). Pale yellow solid
(100 mg, 58%); Rf 0.3 (hexanes-ethyl acetate, 2:1); mp 223 °C; IR
(ATR) 3157, 1682, 1665, 1611, 1472, 799, 777, 762, 739, 691, 656
cm−1; 1H NMR (CDCl3) δ 2.10 (s, 3H), 2.26 (s, 3H), 7.42−7.46 (m,
1H), 7.56−7.61 (m, 1H), 7.82−7.85 (m, 1H), 7.89−7.92 (m, 1H),
8.81 (brs, 1H); 13C NMR (CDCl3, DMSO-d6) δ 20.0 (q), 21.5 (q),
117.4 (q), 122.8 (d), 123.0 (d), 126.9 (d), 129.0 (s), 130.6 (s), 131.4
(d), 136.5 (s), 167.8 (s). Anal. Calcd for C11H11NO: C, 76.28; H, 6.40;
N, 8.09. Found: C, 76.17; H, 6.34; N, 8.01.
3-Cyclopentylidene-2-methylisoindolin-1-one (4c). White
solid (60 mg, 28%); Rf 0.4 (hexanes-ethyl acetate, 2:1); mp 174−
175 °C; IR (ATR) 1684, 1647, 1611, 1472, 804, 772, 689, 669 cm−1;
1H NMR (CDCl3) δ 1.78−1.90 (m, 4H), 2.87−2.91 (m, 2H), 2.95−
2.99 (m, 2H), 3.59 (s, 3H), 7.40−7.45 (m, 1H), 7.53−7.58 (m, 1H),
7.69−7.72 (m, 1H), 7.86−7.89 (m, 1H); 13C NMR (CDCl3) δ 26.4
(t), 27.0 (t), 29.5 (q), 32.7 (t), 33.7 (t), 122.9 (d), 123.1 (d), 127.2
(s), 129.0 (s), 129.3 (s), 129.5 (s), 131.3 (d), 136.6 (s), 167.6 (s).
Anal. Calcd for C14H15NO: C, 78.84; H, 7.09; N, 6.57. Found: C,
78.55; H, 7.03; N, 6.46.
3-(4-tert-Butyl-1-hydroxycyclohexyl)-3-hydroxy-2-methyl-
isoindolin-1-one (3f). White solid (273 mg, 86%); Rf 0.3 (hexanes-
ethyl acetate, 1:2); mp 177 °C; IR (ATR) 3503, 3326, 1655, 1614,
1
1474, 991, 970, 922, 814, 771, 758, 702 cm−1; H NMR (CDCl3) δ
0.70−0.84 (m, 2H), 0.80 (s, 9H), 1.26−1.40 (m, 2H), 1.46−1.53 (m,
1H), 1.54−1.66 (m, 3H), 1.87−1.93 (m, 1H), 2.33 (s, 1H), 2.91 (s,
3H), 4.13 (s, 1H), 7.38−7.42 (m, 1H), 7.48−7.52 (m, 1H), 7.55−7.58
(m, 1H), 7.63−7.66 (m, 1H); 13C NMR (CDCl3) δ 22.1 (t), 22.2 (t),
27.1 (q), 27.7 (t), 32.5 (s), 33.6 (t), 47.6 (d), 76.7 (s), 94.2 (s), 123.1
(d), 124.5 (d), 129.7 (d), 131.5 (d), 132.2 (s), 145.7 (s), 168.4 (s).
Anal. Calcd for C19H27NO3: C, 71.89; H, 8.57; N, 4.41. Found: C,
71.86; H, 8.59; N, 4.40.
3-Hydroxy-3-(1-hydroxycyclopentyl)isoindolin-1-one (3g).
White solid (149 mg, 64%); Rf 0.3 (hexanes-ethyl acetate, 1:5); mp
179−180 °C; IR (ATR) 3200, 3134, 1672, 1618, 1474, 968, 934, 916,
1
883, 870, 826, 771, 745, 700, 691, 650 cm−1; H NMR (DMSO-d6) δ
1.20−1.29 (m, 1H), 1.41−1.71 (m, 6H), 2.00−2.08 (m, 1H), 4.39
(brs, 1H), 6.27 (brs, 1H), 7.42−7.46 (m, 1H), 7.50−7.56 (m, 2H),
7.61−7.65 (m, 1H), 8.56 (brs, 1H); 13C NMR (DMSO-d6) δ 24.3 (t),
24.5 (t), 35.3 (t), 35.8 (t), 84.7 (s), 90.5 (s), 122.1 (d), 124.1 (d),
128.7 (d), 131.6 (d), 132.7 (s), 148.8 (s), 168.9 (s). Anal. Calcd for
C13H15NO3: C, 66.94; H, 6.48; N, 6.00. Found: C, 66.87; H, 6.44; N,
5.92.
3-Hydroxy-3-(1-hydroxycyclohexyl)isoindolin-1-one (3h).
White solid (175 mg, 71%); Rf 0.35 (hexanes-ethyl acetate, 1:5);
mp 207 °C; IR (ATR) 3578, 3385, 3183, 1701, 1686, 1614, 1470, 974,
955, 909, 878, 853, 835, 806, 795, 750, 733, 696, 667 cm−1; NMR
(DMSO-d6) δ 0.90−1.02 (m, 1H), 1.07−1.15 (m, 1H), 1.20−1.56 (m,
7H), 1.76−1.84 (m, 1H), 4.30 (brs, 1H), 6.22 (brs, 1H), 7.42−7.46
(m, 1H), 7.50−7.56 (m, 2H), 7.62−7.66 (m, 1H), 8.52 (brs, 1H); 13C
NMR (DMSO-d6) δ 21.0 (t), 21.1 (t), 25.5 (t), 30.5 (t), 30.8 (t), 74.4
(s), 91.6 (s), 122.2 (d), 124.8 (d), 128.8 (d), 131.5 (d), 132.6 (s),
148.3 (s), 168.9 (s). Anal. Calcd for C14H17NO3: C, 68.00; H, 6.93; N,
5.66. Found: C, 67.78; H, 6.94; N, 5.64.
3-Hydroxy-3-(1-hydroxycycloheptyl)isoindolin-1-one (3i).
White solid (170 mg, 65%); Rf 0.4 (hexanes-ethyl acetate, 1:5); mp
204−205 °C; IR (ATR) 3285, 1665, 1614, 1470, 989, 961, 939, 912,
839, 799, 764, 729, 700, 654 cm−1; 1H NMR (DMSO-d6) δ 1.18−1.60
(m, 10H), 1.65−1.74 (m, 1H), 1.83−1.91 (m, 1H), 4.32 (brs, 1H),
6.22 (brs, 1H), 7.42−7.46 (m, 1H), 7.50−7.56 (m, 2H), 7.65−7.68
(m, 1H), 8.55 (brs, 1H); 13C NMR (DMSO-d6) δ 22.0 (t), 22.5 (t),
29.0 (t), 29.2 (t), 34.8 (t), 35.5 (t), 78.0 (s), 92.0 (s), 122.1 (d), 124.9
(d), 128.8 (d), 131.6 (d), 132.6 (s), 148.5 (s), 168.8 (s). Anal. Calcd
for C15H19NO3: C, 68.94; H, 7.33; N, 5.36. Found: C, 68.96; H, 7.32;
N, 5.33.
3-Cyclopentylideneisoindolin-1-one (4g). Pale yellow solid (76
mg, 38%); Rf 0.4 (hexanes-ethyl acetate, 1:1); mp 247 °C; IR (ATR)
1
3144, 1682, 1672, 1611, 1474, 802, 772, 737, 692 cm−1; H NMR
(CDCl3) δ 1.80−1.96 (m, 4H), 2.59−2.65 (s, 2H), 2.77−2.83 (m,
2H), 7.42−7.47 (m, 1H), 7.56−7.62 (m, 1H), 7.65−7.68 (m, 1H),
7.87−7.91 (m, 1H), 8.04 (brs, 1H); 13C NMR (CDCl3) δ 26.1 (t),
27.3 (t), 30.9 (t), 32.0 (t), 122.4 (d), 123.5 (d), 126.2 (s), 127.3 (d),
128.5 (s), 130.2 (s), 131.7 (d), 136.9 (s), 168.4 (s). Anal. Calcd for
C13H13NO: C, 78.36; H, 6.58; N, 7.03. Found: C, 78.27; H, 7.00; N,
6.96.
3-Cyclohexylideneisoindolin-1-one (4h). Pale yellow solid (109
mg, 51%); Rf 0.35 (hexanes-ethyl acetate, 2:1); mp 214−215 °C; IR
(ATR) 3167, 1678, 1609, 1474, 800, 773, 762, 735, 692, 656 cm−1; 1H
NMR (CDCl3) δ 1.64−1.79 (m, 6H), 2.43−2.49 (m, 2H), 2.79−2.84
(m, 2H), 7.40−7.46 (m, 1H), 7.54−7.60 (m, 1H), 7.88−7.96 (m, 2H),
8.65 (brs, 1H); 13C NMR (CDCl3) δ 26.2 (t), 27.5 (t), 27.7 (t), 29.8
(t), 31.3 (t), 123.5 (d), 123.6 (d), 126.1 (s), 127.2 (s), 127.4 (d),
131.3 (s), 131.8 (d), 137.0 (s), 168.0 (s). Anal. Calcd for C14H15NO:
C, 78.84; H, 7.09; N, 6.57. Found: C, 78.70; H, 7.03; N, 6.49.
3-Cycloheptylideneisoindolin-1-one (4i). Pale yellow solid (84
mg, 37%); Rf 0.35 (hexanes-ethyl acetate, 2:1); mp 164−166 °C; IR
(ATR) 3174, 1680, 1647, 1611, 1472, 962, 858, 799, 758, 748, 727,
1
687, 656 cm−1; H NMR (CDCl3) δ 1.49−2.03 (m, 8H), 2.56−2.67
(m, 2H), 2.80−2.89 (m, 2H), 7.40−7.48 (m, 1H), 7.54−7.61 (m, 1H),
7.79−7.85 (m, 1H), 7.88−7.94 (m, 1H), 8.96 (brs, 1H). 13C NMR
(CDCl3) δ 27.3 (t), 28.8 (t), 29.3 (t), 31.2 (t), 32.4 (t), 123.4 (d),
123.5 (d), 127.3 (d), 128.6 (s), 129.0 (s), 130.8 (s), 131.8 (d), 136.6
(s), 168.3 (s). Anal. Calcd for C15H17NO: C, 79.26; H, 7.54; N, 6.16.
Found: C, 79.15; H, 7.49; N, 6.08.
3-(4-tert-Butyl-1-hydroxycyclohexyl)-3-hydroxyisoindolin-1-
one (3j, 70:30 diastereomeric mixture). White solid (212 mg,
70%); Rf 0.5 (hexanes-ethyl acetate, 1:5); mp 222−223 °C; IR (ATR)
3420, 3270, 1676, 1614, 1468, 982, 957, 930, 880, 797, 773, 754, 710,
3-(4-tert-Butylcyclohexylidene)isoindolin-1-one (4j). White
solid (110 mg, 41%); Rf 0.8 (hexanes-ethyl acetate, 1:5); mp 200−
201 °C; IR (ATR) 3190, 1676, 1665, 1605, 1470, 988, 800, 770, 758,
735, 696 cm−1; 1H NMR (CDCl3) δ 0.89 (s, 9H), 1.20−1.37 (m, 3H),
2.00−2.08 (m, 2H), 2.15−2.28 (m, 2H), 2.71−2.78 (m, 1H), 3.42−
3.49 (m, 1H), 7.42−7.46 (m, 1H), 7.55−7.59 (m, 1H), 7.90−7.92 (m,
1H), 7.93−7.95 (m, 1H), 8.35 (brs, 1H); 13C NMR (CDCl3) δ 27.5
(q), 28.1 (t), 28.3 (t), 29.6 (t), 31.1 (t), 32.5 (s), 47.7 (d), 123.4 (d),
123.6 (d), 125.9 (s), 127.0 (s), 127.4 (d), 131.4 (s), 137.0 (s), 168.0
(s). Anal. Calcd for C18H23NO: C, 80.26; H, 8.61; N, 5.20. Found: C,
80.08; H, 8.53; N, 5.11.
3-Hydroxy-3-(1-hydroxybutyl)isoindolin-1-one (6c, 50:50
diastereomeric mixture). Colorless paste (159 mg, 72%); Rf 0.5
(ethyl acetate); 1H NMR (CDCl3) δ 0.75 (t, 1.5H, J = 7.2 Hz), 0.85 (t,
1.5H, J = 7.2 Hz), 1.16−1.61 (m, 4H), 3.35 (brs, 0.5H), 3.85 (brs,
0.5H), 3.88 (d, 0.5H, J = 10.0 Hz), 4.10−4.13 (m, 0.5H), 4.82 (brs,
0.5H), 5.00 (brs, 0.5H), 7.36−7.42 (m, 1H), 7.46−7.57 (m, 3H),
7.63−7.68 (m, 1H); 13C NMR (CDCl3) δ 13.6 (q), 13.7 (q), 18.9 (t),
19.2 (t), 32.3 (t), 32.6 (t), 74.9 (d), 75.1 (d), 89.8 (s), 90.1 (s), 122.1
(d), 123.2 (d), 123.4 (d), 123.6 (d), 129.2 (d), 129.4 (d), 130.9 (s),
1
694, 660 cm−1; H NMR (DMSO-d6) δ 0.78 (q, 3H), 1.04−1.56 (m,
7.7H), 1.61−1.69 (m, 0.3H), 1.81−1.89 (m, 0.7H), 2.02−2.10 (m,
0.3H), 4.26 (brs, 0.3H), 4.27 (brs, 0.7 H), 6.20 (s, 0.3H), 6.21 (brs,
0.7H), 7.42−7.46 (m, 1H), 7.50−7.56 (m, 2H), 7.63−7.66 (m, 1H),
8.50 (brs, 0.7H), 8.51 (brs, 0.3H); 13C NMR (DMSO-d6) δ 21.7 (t),
21.9 (t), 22.0 (t), 27.5 (q), 27.7 (q), 30.9 (t), 31.3 (t), 32.1 (t), 32.4
(t), 32.7 (t), 73.7 (s), 74.0 (s), 91.3 (s), 92.0 (s), 121.97 (d), 122.04
(d), 124.6 (d), 124.7 (d), 128.6 (d), 128.7 (d), 131.2 (d), 131.4 (d),
132.5 (s), 132.7 (s), 148.3 (s), 148.6 (s), 168.6 (s). Anal. Calcd for
C18H25NO3: C, 71.26; H, 8.31; N, 4.62. Found: C, 71.22; H, 8.35; N,
4.53.
2-Methyl-3-(propan-2-ylidene)isoindolin-1-one (4a). Pale
yellow solid (155 mg, 83%); Rf 0.25 (hexanes-ethyl acetate, 5:1);
mp 110−112 °C; IR (ATR) 1682, 1638, 1609, 943, 822, 760, 691
1
cm−1; H NMR (CDCl3) δ 2.29 (s, 3H), 2.32 (s, 3H), 3.54 (s, 3H),
7.40−7.44 (m, 1H), 7.53−7.57 (m, 1H), 7.81−7.83 (m, 1H), 7.87−
7.89 (m, 1H); 13C NMR (CDCl3) δ 22.7 (q), 23.3 (q), 30.9 (q), 118.4
(s), 122.7 (d), 123.1 (d), 127.0 (d), 129.1 (s), 131.2 (d), 131.2 (d),
12457
dx.doi.org/10.1021/jo402125u | J. Org. Chem. 2013, 78, 12453−12459