T. Opatz, D. Ferenc
FULL PAPER
(300 MHz, [D6]DMSO), COSY (400 MHz, [D6]DMSO): δ = 2.14
NMR (75.5 MHz, [D6]DMSO): δ = 89.9 (C-4), 107.3 (C-4Ј), 113.9
(s, 3 H, Me), 6.46–6.51 (m, 4 H, NH2, 2Ј,6Ј-H), 6.60 (s, 1 H, NH), (C-8a), 114.7 (C-2Ј,6Ј), 119.3 (C-5), 122.1 (C-7), 129.3 (C-8), 131.4
6.86 (AAЈ part of AAЈXXЈ, 2 H, 3Ј,5Ј-H), 7.02–7.09 (m, 2 H, 5-H,
7-H), 7.49 (ddd, J = 8.2, 7.1, 1.3 Hz, 1 H, 6-H), 7.90 ppm (pseudo-
d, J = 7.7 Hz, 1 H, 8-H). 13C NMR (75.5 MHz, [D6]DMSO),
(C-3Ј,5Ј), 134.9 (C-6), 141.3 (C-4a), 147.1 (C-1Ј), 156.0 (C-3),
160.2 ppm (CO). IR (KBr): ν = 3459, 3367, 1709, 1652, 1606, 1554,
˜
1490, 1330, 1288, 815, 764 cm–1. FD-MS (m/z): 330.4 (100) [M]+,
HMQC, HMBC (100.6 MHz, [D6]DMSO): δ = 20.0 (Me), 91.0 (C- 332.4 (71). C15H11BrN2O2 (331.16): C 54.40, H 3.35, N 8.46; found
4), 112.8 (C-2Ј,6Ј), 114.0 (C-8a), 119.7 (C-5), 122.0 (C-7), 125.1 (C-
4Ј), 129.2 (C-8), 129.3 (C-3Ј,5Ј), 134.7 (C-6), 141.7 (C-4a), 145.3
C 54.21, H 3.33, N 8.34.
3-Amino-4-(4-chlorophenylamino)-1H-isochromen-1-one (4i): Yellow
crystals (2.49 g, 87%), m.p. 168 °C (dec.), Rf (cyclohexane/EtOAc
(C-1Ј), 156.0 (C-3), 160.3 ppm (CO). IR (KBr): ν = 3460, 3369,
˜
3284, 1724, 1650, 1606, 1516, 1482, 1295, 811, 757, 697 cm–1. FD-
MS (m/z): 266.3 (100) [M]+, 532.8 (3) [2M]+. C16H14N2O2 (266.29):
C 72.16, H, 5.30, N 10.52; found C 72.34, H 5.23, N 10.65.
1
2:1) = 0.44. H NMR (300 MHz, [D6]DMSO): δ = 6.53–6.62 (m,
4 H, NH2, 2Ј,6Ј-H), 6.99–7.12 (m, 5 H, NH, 5-H, 7-H, 3Ј,5Ј-H),
7.52 (ddd, J = 8.2, 7.1, 1.4 Hz, 1 H, 6-H), 7.91 ppm (ddd, J = 7.9,
1.4, 0.6 Hz, 1 H, 8-H). 13C NMR (75.5 MHz, [D6]DMSO): δ = 90.0
(C-4), 113.9 (C-8a), 114.2 (C-2Ј,6Ј), 119.4 (C-5), 119.9 (C-4Ј), 122.1
(C-7), 128.6 (C-3Ј,5Ј), 129.3 (C-8), 134.9 (C-6), 141.4 (C-4a), 146.8
3-Amino-4-(3-methoxyphenylamino)-1H-isochromen-1-one (4e): Yel-
low crystals (2.49 g, 88%), m.p. 163 °C (dec.), Rf (cyclohexane/
1
EtOAc 2:1) = 0.53. H NMR (300 MHz, [D6]DMSO): δ = 3.63 (s,
3 H, OMe), 6.13–6.22 (m, 3 H, 2Ј-H, 4Ј-H, 6Ј-H), 6.53 (s, 2 H,
NH2), 6.82 (s, 1 H, NH), 6.95 (t, J = 8.1 Hz, 1 H, 5Ј-H), 7.04–7.11
(m, 2 H, 5-H, 7-H), 7.51 (ddd, J = 8.3, 7.1, 1.4 Hz, 1 H, 6-H),
7.90 ppm (ddd, J = 7.9, 1.4, 0.6 Hz, 8-H). 13C NMR (75.5 MHz,
[D6]DMSO): δ = 54.6 (OMe), 90.5 (C-4), 98.8 (C-2Ј), 102.1, 105.6
(C-4Ј, C-6Ј), 113.9 (C-8a), 119.6 (C-5), 122.1 (C-7), 129.2 (C-8),
129.6 (C-5Ј), 134.8 (C-6), 141.6 (C-4a), 149.2 (C-1Ј), 156.0 (C-3),
(C-1Ј), 156.0 (C-3), 160.2 ppm (CO). IR (KBr): ν = 3430, 1723,
˜
1650, 1608, 1556, 1495, 1305, 1089, 816, 766 cm–1. FD-MS (m/z):
286.4 (100) [M]+, 288.4 (34). C15H11ClN2O2 (286.71): C 62.84, H
3.87, N 9.77; found C 63.01, H 3.76, N 9.62.
3-Amino-4-(methylphenylamino)-1H-isochromen-1-one (4j): The
product was purified by flash chromatography on silica gel with
cyclohexane/EtOAc 3:1 as the eluent. Yellow crystals (1.71 g, 64%),
160.27, 160.31 ppm (CO, C-3Ј). IR (KBr): ν = 3409, 3374, 3319,
˜
1
m.p. 163 °C (dec.), Rf (cyclohexane/EtOAc 2:1) = 0.69. H NMR
1714, 1645, 1626, 1551, 1494, 1162, 1093, 845, 748 cm–1. FD-MS
(m/z): 282.4 (100) [M]+. C16H14N2O3 (282.29): C 68.07, H 5.00, N
9.92; found C 67.96, H 5.09, N 9.97.
(300 MHz, [D6]DMSO): δ = 3.16 (s, 3 H, Me), 6.60–6.66 (m, 3 H,
2Ј,6Ј-H, 4Ј-H), 6.70–6.74 (m, 3 H, NH2, 5-H), this multiplet con-
taining 6.71 (br.s, 2 H, NH2), 6.71 (pseudo-d, J = 8.3 Hz, 1 H, 5-
H), 7.04–7.16 (m, 3 H, 7-H, 3Ј,5Ј-H), 7.48 (ddd, J = 8.3, 7.1,
1.4 Hz, 1 H, 6-H), 7.94 ppm (ddd, J = 7.9, 1.4, 0.6 Hz, 1 H, 8-H).
13C NMR (75.5 MHz, [D6]DMSO): δ = 37.2 (Me), 96.4 (C-4),
111.8 (C-2Ј,6Ј), 114.1 (C-8a), 116.2 (C-4Ј), 119.0 (C-5), 122.1 (C-
7), 128.9 (C-3Ј,5Ј), 129.6 (C-8), 134.9 (C-6), 140.8 (C-4a), 148.0 (C-
3-Amino-4-(4-methoxyphenylamino)-1H-isochromen-1-one (4f): Yel-
low crystals (2.21 g, 78%), m.p. 167 °C (dec.), Rf (cyclohexane/
1
EtOAc 2:1) = 0.56. H NMR (300 MHz, [D6]DMSO): δ = 3.62 (s,
3 H, OMe), 6.45–6.55 (m, 5 H, NH, NH2, 2Ј,6Ј-H), 6.70 (AAЈ part
of AAЈBBЈ, 2 H, 3Ј,5Ј-H), 7.04–7.10 (m, 2 H, 5-H, 7-H), 7.50 (ddd,
J = 8.3, 7.0, 1.3 Hz, 1 H, 6-H), 7.90 ppm (dd, J = 8.3, 1.3 Hz, 1 H,
8-H). 13C NMR (75.5 MHz, [D6]DMSO): δ = 55.2 (OMe), 91.5 (C-
4), 113.6, 114.6 (C-2Ј,6Ј, C-3Ј,5Ј), 114.0 (C-8a), 119.7 (C-5), 122.0
(C-7), 129.2 (C-8), 134.7 (C-6), 141.6, 141.8 (C-4a, C-1Ј), 151.3 (C-
1Ј), 155.8 (C-3), 160.2 ppm (CO). IR (KBr): ν = 3472, 3337, 1746,
˜
1640, 1603, 1548, 1483, 1494, 1318, 763, 752 cm–1. FD-MS (m/z):
266.5 (100) [M]+. C16H14N2O2 (266.29): C 72.16, H 5.30, N 10.52;
found C 72.36, H 5.38, N 10.57.
4Ј), 156.1 (C-3), 160.3 ppm (CO). IR (KBr): ν = 3433, 3379, 3292,
˜
3-Amino-4-(2,4-dimethylphenylamino)-1H-isochromen-1-one (4k):
Yellow crystals (1.58 g, 56%), m.p. 151 °C (dec.), Rf (cyclohexane/
EtOAc 2:1) = 0.59. H NMR (300 MHz, [D6]DMSO): δ = 2.12 (s,
1718, 1647, 1606, 1511, 1483, 1233, 1032, 825, 754 cm–1. FD-MS
(m/z) = 282.4 (100) [M+]. C16H14N2O3 (282.29): C 68.07, H 5.00,
N 9.92; found C 68.09, H 4.96, N 9.97.
1
3 H, 4Ј-Me), 2.29 (s, 3 H, 2Ј-Me), 5.92 (s, 1 H, NH), 6.07 (d, J =
8.1 Hz, 1 H, 6Ј-H), 6.49 (br.s, 2 H, NH2), 6.64 (dd, J = 8.1, 2.2 Hz,
1 H, 5Ј-H), 6.85 (d, J = 2.2 Hz, 3Ј-H), 6.95 (pseudo-d, J = 8.3 Hz,
1 H, 5-H), 7.07 (ddd, J = 8.1, 7.1, 1.3 Hz, 1 H, 7-H), 7.50 (ddd, J
= 8.3, 7.1, 1.4 Hz, 1 H, 6-H), 7.91 ppm (dd, J = 8.1, 1.4 Hz, 1 H,
8-H). 13C NMR (75.5 MHz, [D6]DMSO): δ = 17.7 (2Ј-Me), 19.9
(4Ј-Me), 90.9 (C-4), 110.5 (C-6Ј), 113.9 (C-8a), 119.8 (C-5), 122.0
(C-7), 122.2 (C-2Ј), 124.9 (C-4Ј), 126.7 (C-5Ј), 129.1 (C-8), 130.8
(C-3Ј), 134.7 (C-6), 141.8 (C-4a), 142.7 (C-1Ј), 155.9 (C-3),
3-Amino-4-[4-(trifluoromethyl)phenylamino]-1H-isochromen-1-one
(4g): The product was purified by recrystallization from ethyl ace-
tate/cyclohexane. Yellow crystals (2.58 g, 81%), m.p. 152 °C (dec.),
Rf (cyclohexane/EtOAc 2:1)
=
0.40. 1H NMR (300 MHz,
[D6]DMSO): δ = 6.66–6.72 (m, 4 H, NH2, 2Ј,6Ј-H), 7.00 (pseudo-
d, J = 8.1 Hz, 1 H, 5-H), 7.08 (ddd, J = 8.1, 7.1, 1.1 Hz, 1 H, 7-
H), 7.38 (AAЈ part of AAЈXXЈ, 2 H, 3Ј,5Ј-H), 7.47 (s, 1 H, NH),
7.53 (ddd, J = 8.1, 7.1, 1.3 Hz, 1 H, 6-H), 7.92 ppm (pseudo-d, J
= 8.1 Hz, 1 H, 8-H). 13C NMR (75.5 MHz, [D6]DMSO): δ = 89.1
160.4 ppm (CO). IR (KBr): ν = 3462, 1728, 1645, 1608, 1553, 1508,
˜
2
1482, 1332, 1299, 761 cm–1. FD-MS (m/z): 280.4 (100) [M]+, 560.9
(5) [2M]+. C17H16N2O2 (280.32): C 72.84, H 5.75, N 9.99; found C
72.92, H 5.68, N 10.11.
(C-4), 112.4 (br., C-2Ј,6Ј), 113.9 (C-8a), 116.6 (q, J(C,F) = 32 Hz,
1
C-4Ј), 119.2 (C-5), 122.2 (C-7), 125.2 (q, JC,F = 270 Hz, CF3),
3
126.2 (q, JC,F = 3.4 Hz, C-3Ј,5Ј), 129.4 (C-8), 135.0 (C-6), 141.2
(C-4a), 151.2 (C-1Ј), 155.9 (C-3), 160.2 ppm (CO). IR (KBr): ν =
˜
CCDC-251052 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
3369, 1713, 1652, 1619, 1485, 1329, 1158, 1110, 1067, 830 cm–1.
FD-MS (m/z): 320.4 (100) [M]+. C16H11F3N2O2 (320.27): C 60.00,
H 3.46, N 8.75; found C 59.77, H 3.71, N 8.51.
3-Amino-4-(4-bromophenylamino)-1H-isochromen-1-one (4h): Yel-
low crystals (2.45 g, 74%), m.p. 138 °C (dec.), Rf (cyclohexane/
EtOAc 2:1) = 0.26. 1H NMR (300 MHz, [D6]DMSO): δ = 6.53
(AAЈ part of AAЈXXЈ, 2 H, 2Ј,6Ј-H), 6.61 (br.s, 2 H, NH2), 7.00–
7.04 (m, 2 H, NH, 5-H), 7.07 (ddd, J = 8.1, 7.1, 1.0 Hz, 1 H, 7-H),
Acknowledgments
This work was supported by the Fonds der Chemischen Industrie.
7.19 (XXЈ part of AAЈXXЈ, 2 H, 3Ј,5Ј-H), 7.53 (ddd, J = 8.1, 7.1, We thank Dr. H. Detert for kindly providing several anilines, H.
1.3 Hz, 1 H, 6-H), 7.90 ppm (pseudo-d, J = 8.1 Hz, 1 H, 8-H). 13C Kolshorn for the NMR spectroscopic analyses, and Dr. D.
820
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 817–821