1222
Y. Shen et al. / Tetrahedron Letters 49 (2008) 1220–1222
3. Zolfigol, M. A. Synth. Commun. 1999, 29, 905.
Table 2
Solvent effects on the reaction of 1a with NOa
4. (a) Zolfigol, M. A.; Zebarjadian, M. H.; Chehardoli, G.; Keypour, H.;
Salehzadeh, S.; Shamsipur, M. J. Org. Chem. 2001, 66, 3619; (b)
Solvent
Conversion (%)
Yield of 2 (%)
´
`
´
´
Celaries, B.; Parkanyi, C. Synthesis 2006, 2371; (c) Iranpoor, N.;
CCl4
0
0
0
0
Firouzabadi, H.; Pourali, A.-R. Synthesis 2003, 1591.
N(C2H5)3
Benzene
THF
CH2Cl2
CH3CN
CH3OH
H2O
5. (a) Yang, D. S.; Lei, L. D.; Liu, Z. Q.; Wu, L. M. Tetrahedron Lett.
2003, 44, 7245; (b) Liu, Z. Q.; Li, R.; Yang, D. S.; Wu, L. M.
Tetrahedron Lett. 2004, 45, 1565; (c) Liu, Z. Q.; Fan, Y.; Li, R.; Zhou,
B.; Wu, L. M. Tetrahedron Lett. 2005, 46, 1023; (d) Liu, Z. Q.; Zhou,
B.; Liu, Z. L.; Wu, L. M. Tetrahedron Lett. 2005, 46, 1095; (e) Peng,
L. J.; Liu, Z. Q.; Wu, L. M. Tetrahedron Lett. 2007, 48, 7418.
6. Itoh, T.; Nagata, K.; Matsuya, Y.; Miyazaki, M.; Ohsawa, A. J. Org.
Chem. 1997, 62, 3582.
75
>99
90
>99
0
73
93
88
94
0
0
0
a
All the reactions were carried out with 0.15 mmol of 1a in 20 mL
7. Itoh, T.; Nagata, K.; Matsuya, Y.; Miyazaki, M.; Ohsawa, A.
Tetrahedron Lett. 1997, 38, 5017.
solvent for 3 h.
8. Zhao, Y. L.; Stephen, L.; Garrison, C. G.; William, D. J. Phys. Chem.
A 2007, 111, 2200.
R
R
9. Ranu, B. C.; Hajra, A.; Dey, S. S. Org. Process Res. Dev. 2002, 6, 817.
H
EtOOC
H3C
EtOOC
H3C
H
O
1
NH
N
N
O
H
Data for 1a: H NMR (300 MHz, CDCl3) d 1.10 (3H, t, J = 7.0 Hz),
O
O
+
+
H
H
H
2.24 (3H, s), 3.71 (3H, s), 3.98 (2H, q, J = 7.0 Hz), 5.09 (1H, s, N(3)–
H), 6.88 (2H, d, J = 8.5 Hz), 7.15 (2H, d, J = 8.6 Hz), 7.68 (1H, s),
9.17 (1H, s, N(1)–H).
N
H
O
N
H
1
10. Data for representative products 2a: Yellow solid, mp 192–193 °C; IR
(KBr) mmax 3256, 3159, 2976, 1741, 1709, 1648, 1510, 1385, 1304, 1243,
1202, 1097, 1026, 835, 792, 653 cmꢁ1; 1H NMR (200 MHz, CDCl3) d
1.22 (3H, t, J = 7.2 Hz), 2.51 (3H, s, CH3), 3.78 (3H, s), 4.13 (2H, q,
J = 7.2 Hz), 6.45 (1H, s), 6.79 (2H, d, J = 8.6 Hz), 7.24 (2H, d,
J = 8.6 Hz), 8.54 (1H, s, N(1)–H); 13C NMR (75 MHz, CDCl3) d
14.05, 18.26, 53.50, 55.19, 60.73, 106.14, 113.93, 128.68, 129.80,
143.93, 150.51, 159.54, 164.19; MS (EI, 70 eV) m/z 319 (M+), 289,
261, 217, 183, 137, 134, 119, 110, 103, 89, 77; HR-ESI-MS m/z calcd
for C15H18N3O5 (M+Na) 342.1060, found: 342.1058. 1D NOE:
Irradiation of CH3 proton at d 2.51 enhanced N(1)–H proton at d 8.54
by 7%. Compound 2f: Yellow solid, mp 150–151 °C; IR (KBr) mmax
3242, 3140, 2967, 2878, 1722, 1646, 1541, 1391, 1310, 1249, 1219,
R
R
CH3
EtOOC
H3C
EtOOC
H3C
H
O
NH
O
H
CH3
N
H
O
N
H
1
Scheme 3.
compounds because N(1)-aminyl radical intermediate com-
plex is more stable than N(3)-aminyl radical intermediate
complex due to a large conjugated system.
In conclusion, we present herein an approach for regio-
selective N-nitrosation of dihydropyrimidinons with NO.
Its main advantages are readily available starting materials,
convenient performance under mild conditions and high
yields.
1086, 1024, 991, 771 cmꢁ1 1H NMR (300 MHz, CDCl3) d 0.87 (3H,
;
d, J = 6.3 Hz), 0.95 (3H, d, J = 6.3 Hz), 1.15 (1H, m), 1.35 (5H, m),
2.45 (3H, s, CH3), 4.23 (2H, m), 5.76 (1H, t, J = 6.9 Hz), 8.94 (1H, s,
N(1)–H); 13C NMR (75 MHz, CDCl3) d 14.14, 18.12, 21.86, 23.07,
24.28, 43.59, 47.80, 60.73, 107.12, 144.91, 151.51, 164.42; MS (EI,
70 eV) m/z 269 (M+), 239, 224, 212, 183, 154, 137, 110, 96, 68; HR-
ESI-MS m/z calcd for
C12H19N3O4 (M+Na) 292.1268, found:
292.1270; 1D NOE: irradiation of N(1)–H proton at d 8.94 enhanced
CH3 proton at d 2.45 by 6.4%.
Acknowledgment
11. Zolfigol, M. A.; Shirini, F.; Choghamarani, A. G.; Taqian-Nasab, A.;
Keypour, H.; Salehzadeh, S. J. Chem. Res. (S) 2000, 420.
12. Pires, M.; Rossi, M. J.; Ross, D. S. Int. J. Chem. Kinet. 1994, 26,
1207.
13. Lewis, R. S.; Tannenbaum, S. R.; Deen, W. M. J. Am. Chem. Soc.
1995, 117, 3933.
Project No. 20572040 was supported by National Natu-
ral Science Foundation of China.
References and notes
14. (a) Nelsen, J. R.; Eur. Pat. App. EP 301 191 (CA 111: 80345q); (b)
Greenwood, N. N.; Earnshaw, A. In Chemistry of the Elements;
Pergamon Press: Oxford, 1990; Vol. 508, Chapter 11; (c) Upchurch,
G. R.; Welch, G. N.; Loscalzo, J. Adv. Pharmacol. 1995, 34, 343; (d)
von Gratzel, M.; Taniguchi, S.; Henglein, A. Ber. Bunsenges. Phys.
Chem. 1970, 74, 488.
1. (a) White, E. H.; Darbeau, R. W.; Chen, Y.; Chen, D.; Chen, S. J.
Org. Chem. 1996, 61, 7986; (b) Darbeau, R. W.; Gibble, R. E.; Pease,
R. S.; Siso, L. M.; Heurtin, D. J. J. Chem. Soc., Perkin Trans. 2 2001,
1084.
15. Ghosh, K. K.; Satnami, M. L.; Sinha, D.; Vaidya, J. J. Mol. Liq.
2005, 116, 55.
2. Williams, D. L. H. Nitrosation Reactions and the Chemistry of Nitric
Oxide; Elsevier: Amsterdam, 2004; Chapter 2.