An Efficient Approach for the Synthesis of N-1 Substituted Hydantoins
1-Benzylhydantoin (4e): White crystalline solid. M.p. 138–140 °C.
1
IR (KBr): ν = 3180, 3053, 2923, 27.81, 1766, 1691, 1470 cm–1. H
˜
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NMR (400 MHz, [D6]DMSO): δ = 3.83 (s, 2 H), 4.43 (s, 2 H),
7.25–7.38 (m, 4 H), 10.86 (br. s, 1 H, NH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 46.58, 50.40, 128.34, 128.50, 129.28,
135.35, 156.69, 170.46 ppm. HRMS (ESI, MeOH): calcd. for
C10H10N2O2 [M + H]+ 191.0821; found 191.3321.
1-tert-Butylhydantoin (4f): White crystalline solid. M.p. 196–
198 °C. IR (KBr): ν = 3166, 3035, 2979, 2771, 1778, 1692,
˜
1451 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.32 (s, 9 H), 4.00 (s,
2 H), 10.57 (br. s, 1 H NH) ppm. 13C NMR (100 MHz, CDCl3): δ
= 28.12, 49.76, 54.52, 156.22, 170.63 ppm. HRMS (ESI, MeOH):
calcd. for C7H12N2O2 [M + H]+ 157.0977; found 157.2625.
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a) K. H. Hollenbeak, F. J. Schmitz, Lloydia 1977, 40, 479; b)
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1956, 50, 4922d.
1-Phenylhydantoin (4g): White crystalline solid. M.p. 191–192 °C.
IR (KBr): ν = 3173, 3056, 2935, 1831, 1744, 1595, 1503, 1449,
˜
1405 cm–1. 1H NMR (400 MHz, CD3COCD3): δ = 4.46 (s, 2 H), [5]
7.11–7.69 (m, 5 H), 9.97 (br. s, 1 H, NH) ppm. 13C NMR
(100 MHz, CD3COCD3): δ = 51.75, 119.00, 124.31, 129.82, 139.62,
155.31, 170.12 ppm. HRMS (ESI, MeOH): calcd. for C9H8N2O2
[M + H]+ 177.0764; found 177.2992 and 196.3017 [M + Na]+.
a) H. Haruyama, T. Takayama, T. Kinoshita, M. Kondo, M.
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2111; d) S. Mio, M. Shiraishi, S. Sugai, H. Haruyama, S. Sato,
Tetrahedron 1991, 47, 2121; e) S. Mio, Y. Kumagawa, S. Sugai,
Tetrahedron 1991, 47, 2133; f) P. Chemla, Tetrahedron Lett.
1993, 34, 7391; g) P. M. Harrington, M. E. Jung, Tetrahedron
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51, 4635.
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Brandsteller, C. de la Fuente, Y.-B. Kim, L. N. Johnson, S.
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graphos, E. D. Chrysina, N. G. Oikonomakos, G. W. J. Fleet,
Tetrahedron 1996, 52, 10721; d) M. Yamagishi, Y. Yamada, K.
Ozaki, T. Date, K. Okamura, M. Suzuki, K. Matsumoto, J.
Org. Chem. 1992, 57, 1568; e) V. Stella, J. Adv. Drug Deliver.
Rev. 1996, 19, 311; f) B. C. Vanwagenen, R. Larsen, J. H. Card-
ellina, J. Org. Chem. 1993, 58, 335.
1-(4-Methylphenyl)hydantoin (4h): White crystalline solid. M.p.
212–214 °C. IR (KBr): ν = 3172, 3053, 2921, 1740, 1617, 1517,
˜
1444 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 2.26 (s, 3 H),
4.40 (s, 2 H), 7.16–7.48 (m, 4 H) 11.11 (br. s, 1 H, NH) ppm. 13C
NMR (100 MHz, [D6]DMSO): δ = 20.75, 51.42, 118.74, 129.73,
132.90, 136.13, 154.67, 169.94 ppm. HRMS (ESI, MeOH): calcd.
for C10H10N2O2 [M + H]+ 191.0821; found 191.3321.
[6]
1-(3-Methylphenyl)hydantoin (4i): White crystalline solid. M.p. 164–
168 °C. IR (KBr): ν = 3152, 3039, 2925, 1732, 1593, 1495,
˜
1416 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 2.30 (s 3 H), 4.41
(s, 2 H), 6.91–7.42 (m, 4 H) 11.14 (br. s, 1 H, NH) ppm. 13C NMR
(100 MHz, [D6]DMSO): δ = 21.82, 51.49, 115.97, 119.59, 125.86,
129.37, 139.62, 153.97, 168.80 ppm. HRMS (ESI, MeOH): calcd.
for C10H10N2O2 [M + H]+ 191.0821; found 191.3321.
1-(2-Anthracenyl)hydantoin (4j): Greenish solid. M.p. 100 °C. IR
(KBr): ν = 3161, 3047, 1764, 1716, 1626, 1450, 1395 cm–1. 1H
˜
[7]
[8]
a) K. Lavrador, D. Guillerm, G. Guillerm, Bioorg. Med. Chem.
Lett. 1998, 8, 1629; b) F. Tellier, F. Acher, I. Brabet, J.-P. Pin,
R. Azerad, Bioorg. Med. Chem. 1998, 6, 195.
NMR (400 MHz, [D6]DMSO): δ = 4.62 (s, 2 H), 7.45–8.53 (m, 9
H), 11.30 (br. s, 1 H, NH) ppm. HRMS (ESI, MeOH): calcd. for
C17H12N2O2 [M + H]+ 277.0977; found 277.4276.
a) J. A. Monn, M. J. Valli, S. M. Massey, R. A. Wright, C. R.
Salhoff, B. G. Johnson, T. Howe, C. A. Alt, G. A. Rhodes,
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R. Azerad, Bioorg. Med. Chem. 1998, 6, 195.
Methyl 1-Benzylhydantoate (5): White crystalline solid. M.p. 122–
124 °C. IR (KBr): ν = 3460, 3203, 2960, 2925 1749, 1678, 1612,
˜
1495, 1438, 1217 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 3.60
(s, 3 H), 3.89 (s, 2 H), 4.43 (s, 2 H), 6.10 (br. s, 2 H, NH) 7.22–7.34
(m, 5 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 49.28, 52.41,
52.56, 127.18, 128.11, 129.21, 136.56, 159.33, 170.83 ppm. HRMS
(ESI, MeOH): calcd. for C11H14N2O3 222.2405; found 245.3596
[M + Na]+.
4,4Ј-Bis(N-1-hydantoin)diphenyl Ether (10): Creamy solid. M.p.
[9]
a) Urech, Justus Liebigs Ann. Chem. 1873, 165, 99; b) W. T.
Read, J. Am. Chem. Soc. 1922, 44, 1749.
Ͼ300 °C (dec.). IR (KBr): ν = 3169, 3061, 2944, 1762, 1721, 1508,
˜
1446 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 4.43 (s, 4 H),
7.00–7.60 (m, 8 H) 11.13 (br. s, 1 H, NH) ppm. 13C NMR
(100 MHz, [D6]DMSO): δ = 51.64, 119.33, 120.61, 134.20, 153.11,
155.28, 170.93 ppm. HRMS (ESI, MeOH): calcd. for C18H14N4O5
367.1042 [M + H]+; found 367.3242.
[10]
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[12]
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra of products 3–5, 9, and 10.
Acknowledgments
We thank Dr. R. Vijayaraghavan, Director, DRDE Gwalior, for his
keen interest and encouragement.
Eur. J. Org. Chem. 2008, 1910–1916
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