SYNTHESIS
July 1998
1001
1H), 6.48 (d, J = 11.9 Hz, 1H), 6.32 (d, J = 11.9 Hz, 1H), 6.25 (s, 1H),
2.40 (s, 3H).
1H NMR (CDCl3): δ = 8.53 (s, 1H), 7.90–8.20 (m, 4H), 7.32–7.60 (m,
4H), 7.05 (s, 2H).
13C NMR (DMSO-d6): δ = 167.0, 163.9, 160.0, 153.7, 153.1, 142.1,
131.6, 130.5, 126.1, 115.5, 112.6, 106.0, 18.1.
MS: m/z (%) = 273 (M+, 10), 255 (100), 227 (88), 175 (79), 147 (78),
119 (39).
13C NMR (DMSO-d6): δ = 170.8, 135.2, 131.8, 131.7, 131.5, 129.9,
128.4, 128.1, 127.3, 127.1, 126.3, 124.9, 121.5.
MS: m/z (%) = 273 (M+, 100), 246 (5), 217 (21), 190 (29), 178 (24).
Anal.: calcd for C14H11NO5: C, 61.53; H, 4.05; N, 5.12. Found: C,
61.25; H, 4.10; N, 4.86.
N-[4-Methylcoumarin-7-yl]maleimide (3c): yield: 97%; yellow nee-
dles; mp 249.5–251.0°C.
IR (KBr): ν = 1780, 1720, 1620, 1410, 1160 cm–1.
1H NMR (CDCl3): δ = 7.69 (d, J = 8.5 Hz, 1H), 7.47 (d, J = 2.0 Hz,
1H), 7.40 (dd, J = 8.5, 2.0 Hz, 1H), 6.91 (s, 2H), 6.33 (d, J = 1.2 Hz,
1H), 2.46 (d, J = 1.2 Hz, 3H).
N-(2-Fluorenyl)maleamic Acid (2d):10 yield: 96%; yellow solid; mp
271.0–273.0°C.
IR (KBr): ν = 1700, 1630, 1530, 1470, 1420, 1280 cm–1.
1H NMR (DMSO-d6): δ = 13.30 (br, 1H), 10.53 (s, 1H), 7.96 (s, 1H),
7.79 (m, 2H), 7.52–7.58 (m, 2H), 7.20–7.40 (m, 2H), 6.50 (d, J =
12.1 Hz, 1H), 6.29 (d, J =12.1 Hz, 1H), 3.90 (s, 2H).
13C NMR (DMSO-d6): δ = 166.9, 163.4, 144.0, 143.1, 141.0, 137.6,
137.3, 132.0, 130.9, 126.9, 126.4, 125.2, 120.3, 119.7, 118.6, 116.0, 36.7.
MS: m/z (%) = 279 (M+, 12), 261 (51), 204 (6), 181 (100), 164 (16),
152 (28).
13C NMR (DMSO-d6): δ = 169.5, 159.7, 152.9, 135.1, 134.6, 125.9,
122.2, 118.8, 114.6, 114.1, 18.2.
MS: m/z (%) = 255 (M+, 100), 227 (78), 199 (8), 172 (10), 157 (7),
147 (4).
nal.: calcd for C14H9NO4: C, 65.88; H, 3.55; N, 5.48. Found: C, 65.59;
H, 3.77; N, 5.22.
N-(2-Fluorenyl)maleimide (3d):10 yield: 94%; yellow needles; mp
190.0–191.5°C.
N-(3-Fluoranthenyl)maleamic Acid (2e):11 yield: 98%; yellow solid;
mp 179.5–181.5°C.
IR (KBr): ν = 1710, 1490, 1460, 1400, 1170 cm–1.
1H NMR (CDCl3): δ = 7.78-7.90 (m, 2H), 7.25–7.60 (m, 5H), 6.88 (s,
2H), 3.95 (s, 2H).
IR (KBr): ν = 1715, 1640, 1560, 1460 cm–1.
1H NMR (DMSO-d6): δ = 13.32 (br, 1H), 10.69 (s, 1H), 8.27 (d, J =
8.3 Hz, 1H) 7.99–8.18 (m, 5H), 7.74 (t, J = 7.6 Hz, 1H), 7.30–7.45
(m, 2H), 6.76 (d, J = 12.0 Hz, 1H), 6.42 (d, J = 12.0 Hz, 1H).
13C NMR (DMSO-d6): δ = 167.2, 164.2, 138.8, 138.5, 136.3, 134.3,
133.0, 132.4, 132.1, 130.4, 128.0, 127.9, 127.4, 124.0, 123.1, 122.0,
121.7, 121.3, 121.1.
13C NMR (DMSO-d6): δ = 170.2, 143.7, 143.5, 140.7, 140.4, 134.8,
130.2, 127.2, 127.0, 125.7, 125.3, 123.9, 120.4, 120.2, 36.6.
MS: m/z (%) = 261 (M+, 100), 233 (4), 204 (11), 190 (3), 178 (5), 164
(22), 83 (81).
MS: m/z (%) = 315 (M+, 1), 297 (34), 227 (5), 217 (100), 189 (26).
N-(3-Fluoranthenyl)maleimide (3e):11 yield: 86%; pale yellow nee-
dles; mp 270.0–271.0°C.
N-(5-Fluoresceinyl)maleamic Acid (2f): yield: 92%; yellow solid; mp
>300°C.
IR (KBr): ν = 1720, 1490, 1440, 1410, 1380, 1150 cm–1.
1H NMR (CDCl3): δ = 7.84–7.99 (m, 4H), 7.58–7.67 (m, 1H), 7.36–
7.52 (m, 4H), 6.99 (s, 2H).
IR (KBr): ν = 1710, 1680, 1590, 1540, 1470, 1310 cm–1.
1H NMR (DMSO-d6): δ = 12.92 (br, 1H), 10.71 (s, 1H), 10.02 (s, 2H),
8.30 (s, 1H), 7.84 (dd, J = 8.3, 1.5 Hz, 1H), 7.18 (d, J = 8.3 Hz, 1H),
6.49–6.65 (m, 7H), 6.30 (d, J = 11.8 Hz, 1H).
13C NMR (DMSO-d6): δ = 170.7, 139.1, 139.0, 138.1, 137.2, 136.5,
135.1, 132.2, 129.2, 128.4, 128.2, 127.4, 123.4, 122.7, 122.4, 122.3,
121.5, 120.7.
13C NMR (DMSO-d6): δ = 168.6, 164.0, 159.6, 152.0, 147.4, 140.4,
132.3, 129.2, 127.15, 126.8, 124.7, 114.0, 112.7, 109.8, 102.3, 83.2.
MS (SI): m/z (%) = 446 (M + 1, 14), 289 (66), 273 (9), 260 (5), 246 (10).
Anal.: calcd for C24H15NO8: C, 64.72; H, 3.39; N, 3.14. Found: C,
64.88; H, 3.47; N, 2.85.
MS: m/z (%) = 297 (M+, 100), 269 (7), 241 (20), 227 (17), 214 (30).
N-(5-Fluoresceinyl)maleimide (3f):
HMDS (0.324 mg, 2.0 mmol) was added to a stirred suspension of
amic acid 2f (222 mg, 0.5 mmol) and ZnCl2 (136mg, 1.0 mmol) in a
mixture of benzene (27 mL) and DMF (3 mL) and the resulting mix-
ture was refluxed for 2.5 h. After cooling to r.t., the mixture was fil-
tered and filtrate was concentrated under vacuum. The residual DMF
portion was poured into ice-water (50 mL) and the aqueous phase was
acidified to pH 6.0 by adding 0.1 N HCl. On cooling, fluoresceinyl-
maleimide 3f (184 mg) was obtained in 87% yield as an orange-yel-
low solid; mp >300°C.
Synthesis of Maleimide Derivatives 3a–e; General Procedure:
HMDS (0.15 mmol) was added to a stirred suspension of amic acid
2a–e (0.1 mmol) and ZnBr2 (0.1 mmol) in benzene (20 mL) at 65°C.
Immediately a clear solution was formed leaving thick paste at the
bottom of the flask. The mixture was refluxed for the time specified
in the Table and then, after cooling to r.t., it was poured into ice-water
and extracted with EtOAc. The combined extracts were washed suc-
cessively with 0.1 N HCl (30 mL) and brine, dried (Na2SO4) and
evaporated to give pure (>95% as shown by NMR spectra) maleimide
derivative 3a–e.
IR (KBr) ν = 1720, 1600, 1470, 1400, 1390, 1300, 1210 cm–1.
1H NMR (DMSO-d6): δ = 10.20 (s, 2H), 8.00 (d, J = 1.1Hz, 1H), 7.80
(dd, J = 1.6, 8.2 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.28 (s, 2H), 6.55–
6.71 (m, 6H).
13C NMR (DMSO-d6): δ = 169.7, 168.1, 159.7, 152.0, 151.2, 135.0,
133.5, 133.3, 129.2, 126.9, 124.8, 122.1, 112.9, 109.3, 102.4, 83.5.
MS (SI): m/z (%) = 428 (M + 1, 16), 324 (10), 289 (22), 273 (11).
Anal.: calcd for C24H13NO7: C, 67.45; H, 3.06; N, 3.27. Found: C,
67.10; H, 2.89; N, 3.27.
N-(1-Pyrenyl)maleimide (3a):3d yield: 98%; yellow needles; mp
239.0–240.0°C.
IR (KBr): ν = 1710, 1510, 1450, 1400, 1150 cm–1.
1H NMR (CDCl3): δ = 8.00–8.32 (m, 7H), 7.70–7.90 (m, 2H), 7.05 (s,
2H).
13C NMR (DMSO-d6): δ = 170.9, 135.2, 131.3, 130.6, 130.3, 128.7,
128.4, 128.3, 127.3, 127.2, 126.9, 126.2, 126.0, 125.5, 125.2, 124.3,
123.5, 122.2.
P. Y. Reddy would like to thank Aisin Cosmos R&D, Kariya, Nagoya,
Japan for financial support.
MS: m/z (%) = 297 (M+, 100), 269 (20), 243 (25), 227 (24), 214 (55).
N-(1-Anthryl)maleimide (3b):3e ZnCl2 was used as a Lewis acid; pu-
rified by chromatography on silica gel (EtOAc/hexane 1:9); yield:
90%; yellow needles; mp >300°C.
(1) For some recent reviews, see:
Fluorescent and Luminescent Probes for Biological Activity;
Mason, W. T., Ed.; Academic: New York, 1993.
Czarnik, A. W. Acc. Chem. Res. 1994, 27, 302.
IR (KBr): ν = 1720, 1470, 1400, 1150 cm–1.