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4.1.5 General procedure for preparation of substituted 5-
methylenehydantoins
30%) as a white solid. mp > 215 C; H NMR (300 MHz, d6-
DMSO) 10.89 (br s, 4 H), 7.63 (s, 4H), 6.40 (s, 2H).
Hydantoin (500 mg, 5 mmol) was dissolved in H2O (50 mL)
at 70 °C with stirring. Ethanolamine (0.61 mL) was added to the
mixture, which was then heated to reflux. An equimolar quantity
of the appropriate aldehyde solution (5 mmol in 5 mL ethanol)
was added dropwise. The reaction mixture was heated at reflux
for 5 h. The mixture was cooled to room temperature, during
which time the product precipitated. The precipitate was
collected via vacuum filtration, washed several times with H2O
and dried in vacuo. Compounds 6c, 6e-i, and 6k-p were prepared
by the procedure and their NMR spectral data was consistent
with the literature values.13a
4.1.11 General procedure for hydrolysis of benzylhydantions
To a suspension of the benzylhydantoin in H2O (25 mL) was
added solid NaOH (15 equivalents). The mixture was heated at
reflux for 12 h under an N2 atmosphere, during which time the
material went into solution. After cooling to room temperature,
the stirred reaction mixture was quenched with concentrated HCl.
The mixture was extracted several times with ether. The
combined extracts were dried (MgSO4) and concentrated to give
the -keto acid/2-hydroxy-3-arylcinnamic acid. Compounds 7c,
7l14, 8e13c, 8g13d, 8h13c, 8i13c, 8k13f, 8n13f, 8o13e, 8p13f, were
prepared by the procedure and their NMR spectral data was
consistent with the literature values.
4.1.6 5-(3,4-Dimethylphenyl)methylene-2,4-imidazolidinedione
(6j)
The following compounds were prepared by this procedure:
Condensation of 3,4-dimethylbenzaldehyde (671 mg, 5.00
4.1.12 3-(3,4-Dimethylphenyl)-2-hydroxy-2-propenoic acid (8j)
mmol) by the general procedure gave 6j (653 mg, 60%) as a
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white solid. mp > 215 C; H NMR (400 MHz, d6-DMSO) δ
11.08-10.47 (br s, 2H), 7.38 (s, 1H), 7.27 (d, J = 7.9 Hz, 1H),
7.10 (d, J = 7.9 Hz, 1H), 6.30 (s, 1H), 2.19 (s, 3H), 2.17 (s, 3H);
13C NMR (100 MHz, d6-DMSO) δ 166.2, 156.1, 137.5, 137.2,
130.8, 130.4, 130.3, 127.7, 127.4, 109.2, 19.7, 19.5 ppm. Anal.
Calcd. For C12H12N2O2: C, 66.65; H, 5.59; N, 12.93. Found: C,
66.87; H, 5.54; N, 13.10.
Hydrolysis of 6j (424 mg, 1.99 mmol) by the general
procedure gave 8j (206 mg, 55%) as an orange solid. mp 134-136
1
oC; H NMR (400 MHz, d6-DMSO): δ 9.90 (s, 1H), 7.60 (d, J =
7.6 Hz, 2H), 7.33 (d, J = 7.6 Hz, 2H), 6.64 (s, 1H), 2.23 (s, 3H),
2.18 (s, 3H); 13C NMR (100 MHz, d6-DMSO) δ 167.0, 141.4,
136.4, 136.0, 132.9, 130.8, 129.9, 127.4, 110.4, 19.9, 19.7 ppm.
HRMS (FAB): M + Na+, found 215.0675. C11H12O3Na requires
215.0678.
4.1.7 5-[4-(3-Thienyl)phenyl]methylene-2,4-imidazolidinedione
(6r)
4.1.13 3-(4-Bromophenyl)-2-hydroxy-2-propenoic acid (8m)
Condensation of 4-(3-thienyl)benzaldehyde (498 mg, 2.65
mmol) by the general procedure gave 6r (560 mg, 78%) as a
beige solid. mp > 215 oC; 1H NMR (300 MHz, d6-DMSO) δ 8.28
(s, 1H), 7.93 (s, 1H), 7.76 (d, J = 3.9 Hz, 1H), 7.74-7.70 (m, 2H),
7.64 (s, 1H), 7.62-7.57 (m, 2H), 6.34 (s, 1H); 13C NMR (75 MHz,
d6-DMSO) δ 162.0, 157.3, 141.7, 135.6, 132.5, 130.3, 129.1,
128.1, 126.5, 122.6, 122.3, 107.9.
Hydrolysis of 6m (403 mg, 1.51 mmol) by the general
procedure gave 8m (99 mg, 27%) as a white solid. mp 194-196
1
oC; H NMR (400 MHz, d6-DMSO): δ 9.49 (s, 1H), 7.69 (d, J =
8.6 Hz, 2H), 7.51 (d, J = 8.6 Hz, 2H), 6.36 (s, 1H); 13C NMR
(100 MHz, d6-DMSO) δ 166.5, 143.1, 134.7, 131.7, 131.6, 120.5,
108.5 ppm. HRMS (FAB):
C9H7O3BrNa requires 264.9471.
M +
Na+, found 264.9470.
4.1.8
5-(4-(2-Methoxycarbonyl)ethenylphenyl)methylene-2,4-
4.1.14 2-Hydroxy-3-[4-(3-thienyl)phenyl]-2-propenoic acid (8r)
imidazolidinedione (6s)
Hydrolysis of 6r (493 mg, 1.83 mmol) by the general
procedure gave 8r (49 mg, 13%) as a pale yellow solid. mp 194-
196 oC; 1H NMR (400 MHz, d6-DMSO): 9.29 (s, 1H), 7.92 (q, J=
5.5 Hz, 1H), 7.87-7.83 (m, 1H), 7.81 (s, 1H), 7.76 (d, J = 8.2 Hz,
2H), 7.20 (d, J = 8.2 Hz, 2H), 6.39 (s, 1H) 13C NMR (100 MHz,
d6-DMSO): 167.0, 142.5, 141.8, 134.5, 134.4, 130.6, 127.8,
126.7, 126.6, 121.7, 110.0. HRMS (FAB): M + Na+, found
269.0241. C13H10O2SNa+ requires 269.0243.
Condensation of methyl 4’-formylcinnamate (554 mg, 2.91
mmol) by the general procedure gave 6s (369 mg, 47%) as a pale
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yellow solid. mp > 215 C; H NMR (400 MHz, d6-DMSO) δ
11.31 (s, 1H), 10.69 (s, 1H), 7.67 (d, J = 8.0 Hz, 2H), 7.61 (d, J =
8.0 Hz, 2H), 7.53 (d, J = 15.4 Hz, 1H), 6.55 (d, J = 15.4 Hz, 1H),
6.37 (s, 1H), 3.53 (s, 3H); 13C NMR (100 MHz, d6-DMSO) δ
168.1, 165.9, 156.1, 143.6, 135.2, 134.4, 130.2, 129.0, 128.3,
120.1, 107.8, 57.8.
4.1.15
3-[4-(2-Carboxyethenyl)phenyl]-2-hydroxy2-propenoic
4.1.9
5-(3-(2-Methoxycarbonyl)ethenylphenyl)methylene-2,4-
acid (8s)
imidazolidinedione (6t)
Hydrolysis of 6s (369 mg, 1.34 mmol) by the general
procedure gave 8s (43 mg, 14%) as a mustard brown solid. mp >
Condensation of methyl 3’-formylcinnamate (537 mg, 2.44
mmol) by the general procedure gave 6t (409 mg, 53%) as a
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220 C; H NMR (400 MHz, d6-DMSO): 9.55 (s, 1H), 7.75 (d, J
= 8.6 Hz, 2H), 7.61 (d, J = 8.6 Hz, 2H), 7.24 (d, J = 17.2 Hz,
1H), 6.45 (d, J = 17.2 Hz, 1H), 6.38 (s, 1H); 13C NMR (100
MHz, d6-DMSO): δ 168.1, 166.5, 144.0, 143.2, 137.4, 130.0,
128.7, 128.5, 119.4, 108.9. HRMS (FAB): (M – H+) found
233.0453. (C12H10O5 – H+) requires 233.0455.
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yellow solid. mp 232-235 C; H NMR (400 MHz, d6-DMSO) δ
8.27-8.14 (m, 1H), 7.84 (s, 1H), 7.77 (s, 1H), 7.59 (d, J = 16.4
Hz, 1H) 7.57-7.47 (m, 1H), 7.41 (t, J = 6.8 Hz, 1H), 7.25 (t, J =
6.8 Hz), 6.65 (d, J = 16.4 Hz, 1H), 6.39 (s, 1H), 3.20 (s, 3H); 13
C
NMR (100 MHz, d6-DMSO) δ 166.3, 165.8, 156.3, 139.0, 136.5,
134.0, 132.6, 129.8, 129.0, 127.2, 123.4, 121.7, 108.0, 60.3.
HRMS (FAB): (M2 + Na+) found 567.1487. (C14H12N2O4)2Na
requires 567.1486.
4.1.16
3-[3-(2-Carboxyethenyl)phenyl]-2-hydroxy2-propenoic
acid (8t)
From 6t (389 mg, 1.29 mmol), gave 8t (80 mg, 24%) as a
yellow solid. mp 189 oC (dec.); 1H NMR (400 MHz, d6-DMSO):
9.41 (s, 1H), 7.94 (s, 1H), 7.82 (d, J = 7.7 Hz, 1H), 7.53 (d, J =
8.6 Hz, 1H), 7.50 (s, 1H), 7.36 (t, J= 7.7 Hz, 1H), 7.22 (d, J =
16.1 Hz, 1H), 6.46 (d, J = 16.2 Hz, 1H), 6.40 (s, 1H); 13C NMR
(100 MHz, d6-DMSO): 168.0, 166.6, 144.3, 143.0, 138.6, 136.2,
4.1.10
5,5’-(1,4-Phenylenedimethylidyne)bis[2,4-
imidazolidinedione] (6u)
Condensation of 1,4-benzenedicarboxaldehyde (671 mg, 5.00
mmol) by the general procedure was modified by the use of two
equivalents of hydantoin (1.011g, 10.10 mmol) gave 6u (442 mg,