The Journal of Organic Chemistry
Article
temperature, the Knoevenagel adduct of ninhydrin and malononitrile
(1 mmol, 1 equiv) was added to the mixture and stirred at room
temperature for 5 h. After completion of the reaction confirmed by
TLC, the reaction mixture was filtered and washed with ethanol, and
the crude product was purified by column chromatography [silica gel,
n-hexane/EtOAc (1:1)] to yield the pure compound 4.
29.3. MS (EI, 70 eV): m/z = 398 [M+]. Anal. Calcd for C24H22N4O2:
C, 72.34; H, 5.57; N, 14.06. Found: C, 72.47; H, 5.63; N, 13.94
(Z)-5-Amino-3-benzyl-2-(cyclohexylimino)-2H-benzo[f ][1,3]-
oxazino[4,5,6-cd]isoindol-6(3H)-one (4f). Eluent: n-hexane/EtOAc
(1:1). Orange powder (0.24 g, yield 57%); mp 278−280 °C. IR (KBr)
1
(νmax /cm−1): 3463, 3408, 1690, 1617, 1570. H NMR (300 MHz,
DMSO-d6): δ 9.50 (s, 1H, OH), 8.96 (s, 1H, NH),8.35 (d, J = 8.5 Hz,
1H, CH of Ar), 7.84 (d, J = 8.1 Hz, 1H, CH of Ar), 7.76−7.65 (m,
1H, CH of Ar), 7.64−7.53 (m, 1H, CH of Ar), 7.47 (d, J = 8.0 Hz,
2H, 2CH of Ar), 7.39−7.16 (m, 3H, 3CH of Ar), 5.19 (s, 2H, CH2),
3.93−3.80 (s, 1H, CH of cyclohexyl), 1.80−1.10 (m, 10H, CH2 of
cyclohexyl). MS (EI, 70 eV): m/z = 424 [M+]. Anal. Calcd for
C26H24N4O2: C, 73.56; H, 5.70; N, 13.20. Found: C, 73.65; H, 5.61;
N, 13.34. Due to low solubility of product 4f, the 13C NMR not
obtained.
(Z)-5-Amino-2-(tert-butylimino)-3-(4-methylbenzyl)-2H-benzo-
[f ][1,3]oxazino[4,5,6-cd]isoindol-6(3H)-one (4g). Eluent: n-hexane/
EtOAc (1:1). Orange powder (0.32 g, yield 79%); mp 230−232 °C.
IR (KBr) (νmax /cm−1): 3477, 3408, 1690, 1617, 1557. 1H NMR (300
MHz, DMSO-d6): δ 9.51 (s, 1H, OH), 8.89 (s, 1H, NH), 8.36 (d, J =
8.0 Hz, 1H, CH of Ar), 7.80 (d, J = 7.7 Hz, 1H, CH of Ar), 7.71 (t, J
= 7.4 Hz, 1H, CH of Ar), 7.59 (t, J = 7.3 Hz, 1H, CH of Ar), 7.36 (d,
J = 7.7 Hz, 2H, CH of Ar), 7.15 (d, J = 7.7 Hz, 2H, 2CH of Ar), 5.11
(s, 2H, CH2), 2.27 (s, 3H, CH3), 1.37 (s, 9H, C(CH3)3). 13C{1H}
NMR (75 MHz, DMSO-d6): δ 171.2, 168.8, 163.4, 139.4, 137.7,
137.2, 135.9, 133.3, 130.6, 129.2, 128.9, 128.2, 127.8, 122.0, 114.5,
94.7, 53.4, 48.1, 30.3, 21.1. MS (EI, 70 eV): m/z = 412 [M+]. Anal.
Calcd for C25H24N4O2: C, 72.80; H, 5.86; N, 13.58. Found: C, 72.73;
H, 5.82; N, 13.48.
Crystal data for 4g: C25H24N4O2 + EtOH (CCDC 1975717): M =
458.55 g/mol, monoclinic system, space group P21/c, a =
16.809(3)Å, b = 7.3761(15)Å, c = 21.608(4)Å, β = 107.96(3)°, V
= 2548.7(9) Å3, Z = 4, Dc = 1.195 Mg m−3, crystal dimension of 0.35
mm × 0.20 mm × 0.20 mm. The structure was solved by using
SHELXS. The structure refinement and data reduction were carried
out with SHELXL of the X-Step32 suite of programs. The
nonhydrogen atoms were refined anisotropically by full matrix least-
squares on F2 values to final R1 = 0.0892, wR2 = 0.2006 with 319
parameters using 4475 independent reflections (θ range = 1.98−
25.00°). Hydrogen atoms were located from expected geometry and
were not refined.
(Z)-5-Amino-2-(tert-butylimino)-3-(2-chlorobenzyl)-2H-benzo-
[f ][1,3]oxazino[4,5,6-cd]isoindol-6(3H)-one (4h). Eluent: n-hexane/
EtOAc (1:1). Orange powder (0.31 g, yield 72%); mp 223−225 °C.
IR (KBr) (νmax /cm−1): 3483, 3408, 1694, 1617, 1561. 1H NMR (300
MHz, DMSO-d6): δ 9.50 (s, 1H, OH), 8.90 (s, 1H, NH), 8.37 (d, J =
7.7 Hz, 1H, CH of Ar), 7.84 (d, J = 7.2 Hz, 1H, CH of Ar), 7.73 (t, J
= 7.1 Hz, 1H, CH of Ar), 7.61 (t, J = 7.5 Hz, 1H, CH of Ar), 7.49 (d,
J = 7.8 Hz, 1H, CH of Ar), 7.38−7.23 (m, 3H, 3CH of Ar), 5.22 (s,
2H, CH2), 1.29 (s, 9H, C(CH3)3). 13C{1H} NMR (75 MHz, DMSO-
d6) δ171.1, 168.9, 163.8, 139.5, 137.6, 136.2, 133.3, 132.2, 130.7,
129.6, 129.2, 128.9, 128.2, 128.0, 127.9, 127.7, 122.0, 114.4, 94.7,
53.3, 46.4, 30.2. MS (EI, 70 eV): m/z = 432 [M+]. Anal. Calcd for
C24H21ClN4O2: C, 66.59; H, 4.89; N, 12.94. Found: C, 66.71; H,
4.80; N, 12.85.
(Z)-5-Amino-2-(tert-butylimino)-3-methyl-2H-benzo[f ][1,3]-
oxazino[4,5,6-cd]isoindol-6(3H)-one (4a). Eluent: n-hexane/EtOAc
(1:1). Orange powder (0.25 g, yield 78%); mp 222−224 °C. IR (KBr)
1
(νmax /cm−1): 3463, 3408, 1690, 1617, 1557. H NMR (300 MHz,
DMSO-d6): δ 9.45 (s, 1H, OH), 8.85 (s, 1H, NH), 8.37 (d, J = 8.1
Hz, 1H, CH of Ar), 7.84 (d, J = 7.2 Hz, 1H, CH of Ar), 7.79−7.67
(m, 1H, CH of Ar), 7.61 (t, J = 8.4 Hz, 1H, CH of Ar), 3.41 (s, 3H,
CH3), 1.45 (s, 9H, C(CH3)3). 13C{1H} NMR (75 MHz, DMSO-d6):
δ 171.3, 168.7, 163.8, 139.4, 139.2, 135.69, 130.5, 128.7, 128.2, 127.8,
121.9, 114.5, 94.7, 53.4, 32.5, 30.4. MS (EI, 70 eV): m/z = 322 [M+].
Anal. Calcd for C18H18N4O2: C, 67.07; H, 5.63; N, 17.38. Found: C,
67.18; H, 5.55; N, 17.27.
(Z)-5-Amino-2-(tert-butylimino)-3-ethyl-2H-benzo[f ][1,3]-
oxazino[4,5,6-cd]isoindol-6(3H)-one (4b). Eluent: n-hexane/EtOAc
(1:1). Orange powder (0.26 g, yield 77%); mp 228−230 °C. IR (KBr)
1
(νmax /cm−1): 3477, 3408, 1686, 1617, 1566. H NMR (300 MHz,
DMSO-d6): δ 9.47 (s, 1H, OH), 8.88 (s, 1H, NH), 8.35 (d, J = 7.9
Hz, 1H, CH of Ar), 7.82 (d, J = 7.6 Hz, 1H, CH of Ar), 7.72 (t, J =
7.6 Hz, 1H, CH of Ar), 7.59 (t, J = 7.8 Hz, 1H, CH of Ar), 4.10−3.92
(m, 2H, CH2CH3), 1.43 (s, 9H, C(CH3)3), 1.28 (t, J = 6.3 Hz, 3H,
CH2CH3). 13C{1H} NMR (75 MHz, DMSO-d6): δ 171.3, 168.7,
163.1, 139.4, 137.6, 135.8, 130.6, 128.7, 128.2, 127.8, 121.4, 114.5,
94.7, 53.3, 40.2, 30.3, 12.2. MS (EI, 70 eV): m/z = 336 [M+]. Anal.
Calcd for C19H20N4O2: C, 67.84; H, 5.99; N, 16.66. Found: C, 67.75;
H, 5.94; N, 16.72.
(Z)-5-Amino-2-(tert-butylimino)-3-propyl-2H-benzo[f ][1,3]-
oxazino[4,5,6-cd]isoindol-6(3H)-one (4c). Eluent: n-hexane/EtOAc
(1:1). Orange powder (0.23 g, yield 65%); mp 226−228 °C. IR (KBr)
1
(νmax /cm−1): 3477, 3394, 1690, 1591, 1420. H NMR (300 MHz,
DMSO-d6): δ 9.46 (s, 1H, OH), 8.96 (s, 1H, NH), 8.35 (d, J = 7.8
Hz, 1H, CH of Ar), 7.81 (d, J = 7.5 Hz, 1H, CH of Ar), 7.70 (t, J =
7.1 Hz, 1H, CH of Ar), 7.58 (t, J = 7.3 Hz, 1H, CH of Ar), 3.95 (t, J =
6.9 Hz, 2H, NCH2), 1.88−1.72 (m, 2H, CH2CH2), 1.41 (s, 9H,
C(CH3)3), 0.91 (t, J = 7.3 Hz, 3H, CH3). 13C{1H} NMR (75 MHz,
DMSO-d6): δ 171.3, 168.6, 163.5, 139.4, 137.9, 135.8, 130.5, 128.7,
128.1, 127.8, 121.9, 114.4, 94.7, 53.3, 40.0, 47.0, 30.3, 20.1, 11.5. MS
(EI, 70 eV): m/z = 350 [M+]. Anal. Calcd for C20H22N4O2: C, 68.55;
H, 6.33; N, 15.99. Found: C, 68.47; H, 6.40; N, 16.08.
(Z)-5-Amino-2-(tert-butylimino)-3-butyl-2H-benzo[f ][1,3]-
oxazino[4,5,6-cd]isoindol-6(3H)-one (4d). Eluent: n-hexane/EtOAc
(1:1). Orange powder (0.20 g, yield 55%); mp 228−230 °C. IR (KBr)
1
(νmax /cm−1): 3477, 3408, 1686, 1621, 1561. H NMR (300 MHz,
DMSO-d6): δ 9.47 (s, 1H, OH), 8.87 (s, 1H, NH), 8.35 (d, J = 7.9
Hz, 1H, CH of Ar), 7.82 (d, J = 7.5 Hz, 1H, CH of Ar), 7.72 (t, J =
7.2 Hz, 1H, CH of Ar), 7.59 (t, J = 7.5 Hz, 1H, CH of Ar), 3.99 (t, J =
7.1 Hz, 2H, NCH2), 1.74 (p, J = 7.5 Hz, 2H, CH2CH2), 1.42 (s, 9H,
C(CH3)3), 1.39−130 (m,2H, CH2CH3), 0.93 (t, J = 7.3 Hz, 3H,
CH3). 13C{1H} NMR (75 MHz, DMSO-d6): δ 171.3, 168.6, 163.4,
139.4, 137.9, 135.7, 130.5, 128.7, 128.1, 127.8, 121.9, 114.4, 94.6,
53.3, 45.1, 30.3, 28.6, 19.8, 14.1. MS (EI, 70 eV): m/z = 364 [M+].
Anal. Calcd for C21H24N4O2: C, 69.21; H, 6.64; N, 15.37. Found: C,
69.15; H, 6.60; N, 15.33.
Crystal data for 4g: C24H21ClN4O2 (CCDC 1975718): M = 432.90
g/mol, monoclinic system, space group C2/c, a = 33.530(7)Å, b =
7.8764(16)Å, c = 17.472(4)Å, β = 106.11(3)°, V = 4433.1(18) Å3, Z
= 8, Dc = 1.297 Mg m−3, crystal dimension of 0.35 mm × 0.25 mm ×
0.15 mm. The structure was solved by using SHELXS. The structure
refinement and data reduction was carried out with SHELXL of the X-
Step32 suite of programs. The nonhydrogen atoms were refined
anisotropically by full matrix least-squares on F2 values to final R1 =
0.0855, wR2 = 0.1748 with 289 parameters using 3891 independent
reflections (θ range = 2.41−25.00°). Hydrogen atoms were located
from expected geometry and were not refined.
(Z)-5-Amino-3-benzyl-2-(tert-butylimino)-2H-benzo[f ][1,3]-
oxazino[4,5,6-cd]isoindol-6(3H)-one (4e). Eluent: n-hexane/EtOAc
(1:1). Orange powder (0.32 g, yield 79%); mp 231−233 °C. IR (KBr)
1
(νmax /cm−1): 3477, 3408, 1690, 1626, 1557. H NMR (300 MHz,
DMSO-d6): δ 9.50 (s, 1H, OH), 8.89 (s, 1H, NH),8.35 (d, J = 6.7 Hz,
1H, CH of Ar), 7.81 (d, J = 8.0 Hz, 1H, CH of Ar), 7.76−7.65 (m,
1H, CH of Ar), 7.65−7.53 (m, 1H, CH of Ar), 7.46 (d, J = 6.8 Hz,
2H, 2CH of Ar), 7.40−7.24 (m, 3H, 3CH of Ar), 5.15 (s, 2H, CH2),
(Z)-5-Amino-2-(tert-butylimino)-3-(2,6-dimethoxyphenethyl)-
2H-benzo[f ][1,3]oxazino[4,5,6-cd]isoindol-6(3H)-one (4i). Eluent:
n-hexane/EtOAc (1:1). Red powder (0.38 g, yield 80%); mp 256−
1.36 (s, 9H, C(CH3)3). 13C{1H} NMR (75 MHz, DMSO-d6
+
CDCl3): δ 170.2, 167.9, 162.5, 138.5, 136.8, 135.3, 135.0, 129.7,
128.5, 127.9, 127.7, 127.2, 127.1, 126.8, 121.1, 113.5, 93.8, 52.5, 47.4,
1
258 °C. IR (KBr) (νmax /cm−1): 3463, 3408, 1686, 1621, 1566. H
2250
J. Org. Chem. 2021, 86, 2244−2253