V. Zuliani et al. / European Journal of Medicinal Chemistry 44 (2009) 3471–3479
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6.1.4.4. (Z)-5-(3-Chlorobenzylidene)-1-phenethylhydantoin (4). Mp
153–155 ꢁC. 1H NMR (DMSO-d6; 300 MHz)
2.30 (t, 2H), 3.62 (t,
6.1.4.15. (Z)-5-Benzylidene-1-benzylhydantoin (15). Mp 132–133 ꢁC.
1H NMR (DMSO-d6; 300 MHz)
4.66 (s, 2H), 6.55–6.59 (m, 2H), 6.64
d
d
2H), 6.67–6.70 (m, 3H), 7.14–7.19 (m, 3H), 7.39–7.44 (m, 1H), 7.48–
7.50 (m, 2H), 7.55 (d, 1H), 11.30 (s, 1H). MS-APCI m/z: 327.3, 325.3
[M-H]ꢂ. Anal. C18H15N2O2Cl (C, H, N).
(s, 1H), 7.10–7.18 (m, 5H), 7.26–7.33 (m, 3H), 11.67 (br s, 1H). MS-
APCI m/z: 277.2 [M-H]ꢂ. Anal. C17H14N2O2 (C, H, N).
6.1.4.16. (E)-5-(4-Hydroxybenzylidene)-1-benzylhydantoin (16). Mp
6.1.4.5. (E)-5-(3-Hydroxybenzylidene)-1-phenethylhydantoin (5). Mp
223–226 ꢁC. 1H NMR (CDCl3; 300 MHz)
d 4.86 (s, 2H), 6.28 (s, 1H),
6.70 (d, J ¼ 8.7 Hz, 2H), 7.23–7.38 (m, 5H), 7.79 (d, J ¼ 8.7 Hz, 2H),
9.83 (br s, 1H), 11.43 (br s, 1H). MS-APCI m/z: 293.2 [M-H]ꢂ. Anal.
C17H14N2O3 (C, H, N).
185–187 ꢁC. 1H NMR (DMSO-d6; 300 MHz)
d
2.88 (t, 2H), 3.87 (t, 2H),
6.33 (s,1H), 6.70–6.73 (m,1H), 7.10–7.34 (m, 8H), 9.36 (s,1H),11.23 (s,
1H). MS-APCI m/z: 307.2 [M-H]ꢂ. Anal. C18H15N2O3 (C, H, N).
6.1.4.6. (Z)-5-(3-Hydroxybenzylidene)-1-phenethylhydantoin (6). Mp
6.1.4.17. (Z)-5-(4-Hydroxybenzylidene)-1-benzylhydantoin (17). Mp
192–195 ꢁC. 1H NMR (DMSO-d6; 300 MHz)
d
2.31 (t, 2H), 3.66 (t, 2H),
233–235 ꢁC. 1H NMR (DMSO-d6; 300 MHz)
d 4.71 (s, 2H), 6.57 (s,
6.66 (s, 1H), 6.69–6.86 (m, 1H), 7.14–7.29 (m, 8H), 9.62 (s, 1H), 11.36
1H), 6.65–6.72 (m, 4H), 7.05 (d, J ¼ 8.4 Hz, 2H), 7.15–7.17 (m, 3H),
9.78 (s, 1H), 11.56 (s, 1H). MS-APCI m/z: 293.3 [M-H]ꢂ. Anal.
C17H14N2O3 (C, H, N).
(br s, 1H). MS-APCI m/z: 307.3 [M-H]ꢂ. Anal. C18H15N2O3 (C, H, N).
6.1.4.7. (E)-5-(4-Hydroxybenzylidene)-1-phenethylhydantoin (7). Mp
213–215 ꢁC. 1H NMR (DMSO-d6; 300 MHz)
d
2.86 (t, J ¼ 7.2 Hz, 2H),
6.1.4.18. (E)-5-Benzylidene-1-n-butylhydantoin
(18). Mp
145–
3.86 (t, J ¼ 7.3, 2H), 6.37 (s, 1H), 6.75 (d, J ¼ 9.0 Hz, 1H), 7.18–7.33 (m,
5H), 7.85 (d, J ¼ 8.7 Hz, 2H), 9.84 (br s,1H),11.19 (br s, 1H). MS-CI m/z:
308 [M þ H]þ. Anal. C18H15N2O3 (C, H, N).
148 ꢁC. 1H NMR (DMSO-d6; 300 MHz)
d
0.99 (t, J ¼ 7.2 Hz, 3H), 1.39–
1.46 (m, 2H), 1.61–1.71 (m, 2H), 3.70 (t, J ¼ 7.2 Hz, 2H), 6.26 (s, 1H),
7.28–7.42 (m, 3H), 7.87 (d, J ¼ 7.5 Hz, 2H). MS-CI m/z: 243.2 [M-H]ꢂ.
Anal. C14H16N2O2 (C, H, N).
6.1.4.8. (Z)-5-(4-Hydroxybenzylidene)-1-phenethylhydantoin (8). Mp
1
210–212 ꢁC. H NMR (DMSO-d6; 300 MHz)
d
2.29 (t, J ¼ 7.8 Hz, 2H),
6.1.4.19. (Z)-5-Benzylidene-1-n-butylhydantoin (19). Mp 86–87 ꢁC.
3.70 (t, J ¼ 7.8, 2H), 6.67 (s, 1H), 6.70–6.72 (m, 2H), 6.85 (d, J ¼ 8.1 Hz,
2H), 7.14–7.19 (m, 3H), 7.28 (d, J ¼ 8.7 Hz, 2H), 9.83 (br s, 1H),
11.31 (br s, 1H). MS-APCI m/z: 307.2 [M-H]ꢂ. Anal. C18H15N2O3
(C, H, N).
1H NMR (DMSO-d6; 300 MHz)
d
2.27 (t, J ¼ 7.4 Hz, 2H), 3.69 (t,
J ¼ 7.4 Hz, 2H), 3.82 (s, 3H), 6.64–6.69 (m, 2H), 6.71 (s, 1H), 7.04 (d,
J ¼ 8.2 Hz, 2H), 7.10–7.20 (m, 3H), 7.40 (d, J ¼ 8.6 Hz, 2H), 11.25 (s,
1H). MS-APCI m/z: 243.0 [M-H]ꢂ. Anal. C14H16N2O2 (C, H, N).
6.1.4.9. (E)-5-(4-Methoxybenzylidene)-1-phenethylhydantoin (9). Mp
6.1.4.20. (E)-5-(4-Chlorobenzylidene)-1-n-butylhydantoin (20). Mp
1
190–191 ꢁC.; H NMR (DMSO-d6; 300 MHz)
d
2.88 (t, J ¼ 7.1 Hz, 2H),
113–115 ꢁC. 1H NMR (DMSO-d6; 300 MHz)
d
0.91 (t, J ¼ 7.2 Hz,
3.87 (t, J ¼ 7.3 Hz, 2H), 3.91 (s, 3H), 6.41 (s,1H), 6.94 (d, J ¼ 9.0 Hz, 2H),
7.20–7.33 (m, 5H), 7.92 (d, J ¼ 8.9 Hz, 2H), 11.25 (br s, 1H). MS-CI m/z:
323.1 [M þ H]þ. Anal. C19H18N2O3 (C, H, N).
3H), 1.28–1.35 (m, 2H), 1.50–1.57 (m, 2H), 3.63 (t, J ¼ 7.0 Hz, 2H),
6.47 (s, 1H), 7.42 (d, J ¼ 8.5 Hz, 2H), 7.94 (d, J ¼ 8.5 Hz, 2H), 11.39
(br s, 1H). MS-APCI m/z: 277.2 [M-H]ꢂ, 279.1. Anal. C14H15N2O2Cl
(C, H, N).
6.1.4.10. (E)-N-(4-(3-Phenethylhydantoin-4-ylidene)methyl)pheny-
lacetamide (10). Mp 255–256 ꢁC. 1H NMR (DMSO-d6; 300 MHz)
6.1.4.21. (Z)-5-(4-Chlorobenzylidene)-1-n-butylhydantoin (21). Mp
d
2.06 (S, 3H), 2.87 (t, J ¼ 7.0 Hz, 2H), 3.87 (t, J ¼ 7.0 Hz, 2H), 6.39 (s,
103–105 ꢁC. 1H NMR (DMSO-d6; 300 MHz)
d
0.57 (t, J ¼ 7.0 Hz, 3H),
1H), 7.18–7.33 (m, 5H), 7.56 (d, J ¼ 8.5 Hz, 2H) 7.86 (d, J ¼ 8.5 Hz,
2H), 10.07 (s, 1H), 11.27 (s, 1H). MS-APCI m/z: 347.06 [M-H]ꢂ. Anal.
C20H19N3O3 (C, H, N).
0.79–0.86 (m, 2H), 0.89–1.02 (m, 2H), 3.42 (t, J ¼ 7.1 Hz, 2H), 6.65 (s,
1H), 7.41 (d, J ¼ 8.5 Hz, 2H), 7.49 (d, J ¼ 8.5 Hz, 2H), 11.51 (br s, 1H).
MS-APCI m/z: 277.1 [M-H]ꢂ, 279.1. Anal. C14H15N2O2Cl (C, H, N).
6.1.4.11. (Z)-N-(4-(3-Phenethylhydantoin-4-ylidene)methyl)phenyla-
6.1.4.22. (E)-5-Benzylidene-1-phenylhydantoin
(22). Mp
235–
cetamide (11). Mp 184–185 ꢁC. 1H NMR (DMSO-d6; 300 MHz)
d
2.09
240 ꢁC. 1H NMR (CD3OD; 300 MHz)
d
6.16 (s, 1H), 7.30–7.36 (m, 3H),
(S, 3H), 2.27 (t, J ¼ 7.0 Hz, 2H), 3.70 (t, J ¼ 7.0 Hz, 2H), 6.66–6.70 (m,
3H), 7.12–7.14 (m, 3H), 7.39 (d, J ¼ 8.5 Hz, 2H) 7.67 (d, J ¼ 8.5 Hz, 2H),
10.14 (s, 1H), 11.38 (s, 1H). MS-APCI m/z: 347.06 [M-H]ꢂ. Anal.
C20H19N3O3 (C, H, N).
7.43–7.46 (m, 2H), 7.53–7.55 (m, 1H) 7.59–7.63 (m, 2H) 7.80–7.83
(m, 2H). MS-APCI m/z: 262.7 [M-H]ꢂ. Anal. C16H12N2O2 (C, H, N).
6.1.4.23. (Z)-5-Benzylidene-1-phenylhydantoin
(23). Mp
190–
194 ꢁC. 1H NMR (CD3OD; 300 MHz)
d
6.85–6.88 (m, 3H), 6.94 (t,
6.1.4.12. (E)-5-Benzylidene-1-(3-chlorophenethyl)hydantoin (12). Mp
J ¼ 7.8 Hz, 2H), 7.04–7.09 (m, 3H), 7.14–7.16 (m, 3H). MS-APCI m/z:
147–149 ꢁC. 1H NMR (DMSO-d6; 300 MHz)
d
2.91 (t, J ¼ 7.2 Hz, 2H),
262.9 [M-H]ꢂ. Anal. C16H12N2O2 (C, H, N).
3.90 (t, J ¼ 7.2 Hz, 2H), 6.51 (s, 1H), 7.18–7.47 (m, 7H), 7.85 (d,
J ¼ 7.2 Hz, 2H), 11.33 (s, 1H). MS-APCI m/z: 327.3, 325.3 [M-H]ꢂ. Anal.
C18H15N2O2Cl (C, H, N).
6.1.4.24. (E)-5-Benzylidene-1-n-hexylhydantoin (24). Mp 105–
108 ꢁC. 1H NMR (DMSO-d6; 300 MHz)
(m, 6H), 1.54 (m, 2H), 3.63 (t, J ¼ 7.2 Hz, 2H), 6.48 (s, 1H), 7.30–7.40
(m, 3H), 7.91 (d, J ¼ 7.0 Hz, 2H), 11.33 (br s, 1H). MS-APCI m/z: 271.2
[M-H]ꢂ. Anal. C16H20N2O2 (C, H, N).
d
0.86 (t, J ¼ 6.7 Hz, 3H), 1.29
6.1.4.13. (Z)-5-Benzylidene-1-(3-chlorophenethyl)hydantoin (13). Mp
153–155 ꢁC. 1H NMR (DMSO-d6; 300 MHz)
3.64 (t, J ¼ 7.6 Hz, 2H), 6.56 (s, 1H), 6.65 (d, 1H), 6.76 (s, 1H), 7.18–7.20
(m, 2H), 7.42–7.51 (m, 5H), 11.49 (s, 1H). MS-APCI m/z: 327.2, 325.3
[M-H]ꢂ. Anal. C18H15N2O2Cl (C, H, N).
d
2.26 (t, J ¼ 7.5 Hz, 2H),
6.1.4.25. (Z)-5-Benzylidene-1-n-hexylhydantoin
(DMSO-d6; 300 MHz)
(25). 1H
NMR
d
0.70 (t, J ¼ 7.0 Hz, 3H), 0.72–1.09 (m, 8H),
3.40 (t, J ¼ 7.3 Hz, 2H), 6.69 (s, 1H), 7.32–7.43 (m, 5H), 11.46 (br s,
6.1.4.14. (E)-5-Benzylidene-1-benzylhydantoin
(14). Mp
181–
1H). MS-APCI m/z: 271.2 [M-H]ꢂ. Anal. C16H20N2O2 (C, H, N).
183 ꢁC. 1H NMR (CDCl3; 300 MHz)
d
4.92 (s, 2H), 6.22 (s, 1H), 7.25–
7.40 (m, 8H), 7.74 (d, J ¼ 7.8 Hz, 2H), 8.57 (br s, 1H). MS-APCI m/z:
6.1.4.26. (E)-5-Benzylidene-1-methylhydantoin
(26). Mp
188–
277.1 [M-H]ꢂ. Anal. C17H14N2O2 (C, H, N).
190 ꢁC. 1H NMR (CD3OD; 300 MHz)
d
3.18 (s, 3H), 6.41 (s, 1H), 7.32–