Synthesis of Diels–Alder adducts of N-arylmaleimides by a multicomponent reaction
833
(3.646 mmol); the product was recrystallized from a cold
mixture of CH2Cl2/n-hexane, leading to a white powder in
76.9% yield (399.9 mg, 1.402 mmol). M.p.: 197–199 °C;
Rf = 0.15 (n-hexane/AcOEt 6:4); UV–Vis (CH2Cl2): kmax
(e) = 234.4 1.5 (10,199.5) nm (mol-1 dm3 cm-1); IR
Ethyl 4-[(3aR*,4S*,7R*,7aS*)-1,3,3a,4,7,7a-hexahydro-
1,3-dioxo-4,7-methano-2H-isoindol-2-yl]benzoate
(9b, C18H17NO4)
From the general method, with 250 mg of 3b (1.51 mmol),
148 mg of maleic anhydride (1.51 mmol), and 0.25 cm3 of
cyclopentadiene (8, 3.02 mmol); the product was recrys-
tallized from a cold mixture of CH2Cl2/n-hexane, leading
to a beige powder in 75.2% yield (354 mg, 1.14 mmol).
M.p.: 130–132 °C; Rf = 0.46 (n-hexane/AcOEt 6:4); IR
-1
(KBr): m = 3,451, 2,929, 1,706, 1,454 cm
;
1H NMR
ꢀ
3
(500 MHz, CDCl3): d = 8.13 (1H, d, J = 7.50 Hz), 8.01
(1H, s), 7.58 (1H, t), 7.51 (1H, d, 3J = 8.55 Hz), 5.65 (1H,
br), 3.32 (1H, ddd, 3J = 8.20 Hz, 3J = 7.25 Hz, 3J =
2.62 Hz), 3.26 (1H, ddd, 3J = 8.10 Hz, 3J = 7.94 Hz,
3J = 2.62 Hz), 2.67 (1H, ddd, 2J = 15.38 Hz, 3J =
7.25 Hz, 3J = 2.25 Hz), 2.61 (1H, dd, 2J = 15.38 Hz,
3J = 7.94 Hz), 2.34 (1H, dd, 2J = 15.50 Hz, 3J =
7.50 Hz), 2.30 (1H, m), 1.80 (3H, s) ppm; 13C NMR
(125 MHz, CDCl3): d = 179.5, 179.3, 171.0, 136.8,
132.7, 131.9, 130.8, 130.4, 129.6, 128.4, 120.4, 40.0,
39.6, 29.1, 24.7, 23.7 ppm; HRMS (EI): m/z calculated
for C16H15NO4 [M?] 235.1001, found 285.1001.
ꢀ
(KBr): m = 2,941, 1,731, 1,609, 1,510, 1,478, 1,278, 857,
1
768 cm-1; H NMR (300 MHz, CDCl3): d = 8.08 (2H, d,
3J = 8.40 Hz), 7.23 (2H, d, J = 8.40 Hz), 6.25 (2H, br),
3
3
4.36 (2H, q, J = 7.10 Hz), 3.49 (2H, m), 3.43 (2H, dd,
3J = 3.00 Hz, J = 1.50 Hz), 1.77 (1H, d, J = 8.85 Hz),
1.60 (1H, d, 2J = 8.85 Hz), 1.36 (3H, t, 3J = 7.10 Hz)
ppm; 13C NMR (75 MHz, CDCl3): d = 176.6, 165.9,
135.9, 134.9, 134.88, 130.5, 126.6, 61.4, 52.5, 46.1, 46.09,
14.5 ppm.
4
2
(3aR*,4S*,7R*,7aS*)-3a,4,7,7a-Tetrahydro-2-phenyl-4,
7-methano-1H-isoindole-1,3(2H)-dione (9e)
Ethyl 3-[(3aR*,7aS*)-1,3,3a,4,7,7a-hexahydro-5-methyl-
1,3-dioxo-2H-isoindol-2-yl]benzoate (4d, C18H19NO4)
From the general method, with 250 mg of 3d (1.513 mmol),
148.4 mg of 1 (1.513 mmol), and 0.30 cm3 of 2 (3.027
mmol); the product was dissolved with CH2Cl2 and filtered
through a layer of silica gel. The solvent was removed under
vacuum in a rotary evaporator, leaving a translucent yellow
liquid in 96.2% yield (456.2 mg, 1.456 mmol). Rf = 0.54
(n-hexane/AcOEt 6:4); UV–Vis (CH2Cl2): kmax (e) =
231.3 1.4 (10,965.1) nm (mol-1 dm3 cm-1); IR (CHCl3):
From the general method, with 0.25 cm3 of 3e
(2.68 mmol), 263 mg of maleic anhydride (2.68 mmol),
and 0.45 cm3 of cyclopentadiene (8, 5.36 mmol); the
product was recrystallized from a cold mixture of
CH2Cl2/n-hexane, leading to a yellow powder in 83.5%
yield (536 mg, 2.24 mmol). M.p.: 136–138 °C (Ref. [45]
143 °C).
(3aR*,4S*,7R*,7aS*)-2-(4-Fluorophenyl)-3a,4,7,7a-tetra-
hydro-4,7-methano-1H-isoindole-1,3(2H)-dione (9f)
From the general method, with 0.22 cm3 of 3f
(2.25 mmol), 220 mg of maleic anhydride (2.25 mmol),
and 0.40 cm3 of cyclopentadiene (8, 4.50 mmol); the
product was recrystallized from a cold mixture of AcOEt/
n-hexane, leading to a transparent crystals in 89.9% yield
(520 mg, 2.02 mmol). M.p.: 172–174 °C (Ref. [46]
170–173 °C).
m = 3,451, 2,938, 1,712, 1,450 cm-1; 1H NMR (500 MHz,
ꢀ
CDCl3): d = 7.98 (1H, d, 3J = 9.15 Hz), 7.86 (1H, s), 7.45
(1H, t), 7.36 (1H, d, 3J = 9.15 Hz), 5.54 (1H, br), 4.29 (2H,
q), 3.18 (1H, ddd, 3J = 9.38 Hz, 3J = 6.80 Hz, 3J =
2.50 Hz), 3.12 (1H, ddd, 3J = 9.38 Hz, 3J = 6.80 Hz,
3J = 2.50 Hz), 2.54 (1H, ddd, 2J = 15.62 Hz, 3J =
6.80 Hz, 3J = 2.50 Hz), 2.48 (1H, dd, 2J = 15.50 Hz,
3J = 2.50 Hz), 2.20 (1H, dd, 2J = 15.50 Hz, 3J =
7.13 Hz), 2.16 (1H, m), 1.69 (3H, s), 1.30 (3H, t) ppm;
13C NMR (125 MHz, CDCl3): d = 179.3, 179.2, 163.7,
136.7, 132.6, 131.8, 131.0, 129.6, 129.3, 127.8, 120.4,
61.5, 39.9, 39.5, 29.0, 24.6, 23.6, 14.5 ppm; HRMS (EI):
m/z calculated for C18H19NO4 [M?] 313.1314, found
313.1324.
General method for the preparation
of the N-arylmaleamic acids 5a–5d
The aniline 3a–3d (2 g) and approximately 1.1 equivalents
of maleic anhydride (1) were dissolved separately in
100-cm3 round-bottom flasks fitted with rubber septa, with
approximately 20 cm3 of anhydrous THF each. The flask
with the aniline, which also contained a magnetic stirrer,
was introduced into an ice bath at 0 °C, and the solution of
maleic anhydride was slowly added through a cannula. The
mixture was stirred for 16 h at r.t., after which the product
was filtered and washed twice with 20 cm3 of n-hexane and
characterized by spectroscopy. No further purification was
carried out.
(3aR*,7aS*)-3a,4,7,7a-Tetrahydro-5-methyl-2-phenyl-1H-
isoindole-1,3(2H)-dione (4e)
From the general method, with 0.25 cm3 of 3e (2.68
mmol), 263 mg of 1 (2.68 mmol), and 0.55 cm3 of 2
(5.36 mmol); the product was recrystallized from a cold
mixture of CH2Cl2/n-hexane, leading to a yellow powder in
73.2% yield (474 mg, 1.96 mmol). M.p.: 83–85 °C (Ref.
[44] 85–87 °C).
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