PAPER
New 4-Nitrosophenyl-1,4-dihydropyridines of Pharmacological Interest
2783
1H NMR (300 MHz, CDCl3): = 1.20 (t, 6 H, J = 7.2 Hz, CH2CH3),
2.36 (s, 6 H, RCH3), 4.10 (q, 4 H, J = 3.8 Hz, CH2CH3), 5.10 (s, 1
H, CH), 5.70 (s, 1 H, NH), 7.67–7.70 (m, 4 H, ArH).
13C NMR (75 MHz, CDCl3): = 13.23 (2 C), 18.58 (2 C), 38.85,
58.93, 102.53, 118.13, 119.82, 127.55, 128.04, 134.54, 143.68,
148.69, 165.46, 165.80, 166.25, 167.67.
Yield. 30%; mp 147 ºC.
IR (KBr): 3335, 2951, 1704, 1650, 1488, 1435, 1020 cm–1.
1H NMR (300 MHz, CDCl3): = 2.37 (s, 6 H, RCH3), 3.65 (s, 6 H,
OCH3), 5.10 (s, 1 H, CH), 5.86 (s, 1 H, NH), 7.52 (d, 2 H, J = 8.6
Hz, ArH), 7.79 (d, 2 H, J = 8.6 Hz, ArH).
13C NMR (75 MHz, CDCl3): = 18.33 (2 C), 19.56, 40.01, 51.07,
58.38 (2 C), 102.73, 121.18 (2 C), 128.45 (2 C), 144.87, 155.32 (2
C), 165.47, 167.44.
Anal. Calcd for C19H22O5N2: C, 63.68; H, 6.19; N, 7.82. Found C,
63.52; H, 6.48; N, 7.46.
Anal. Calcd for C17H18O5N2: C, 61.81; H, 5.49; N, 8.48. Found: C,
62.22; H, 5.63; N, 8.61.
4-(3-Nitrosophenyl)-2,6-dimethyl-3,5-diisopropyloxycarbonyl-
1,4-dihydropyridine
Yield: 40%; mp 131 ºC.
The meta- and para-nitroso derivatives may be stored in the men-
tioned conditions for a period of about one month without apprecia-
ble decomposition. The ortho-derivative was very unstable and it
was not possible to isolate it in pure form from the above mentioned
conditions.
IR (KBr): 3348, 2980, 1700, 1648, 1489, 1370, 1296, 1216, 1105,
1016, 750 cm–1.
1H NMR (300 MHz, CDCl3):
CH(CH3)2], 1.18 [d, 6 H, J = 6.2 Hz, CH(CH3)2], 2.27 (s, 6 H,
RCH3), 4.86 [sept, 2 H, J = 6.2 Hz, CH(CH3)2], 5.02 (s, 1 H, CH),
5.82 (s, 1 H, NH), 7.19–7.70, (m, 4 H, ArH).
13C NMR (75 MHz, CDCl3): = 18.55, 20.77, 21.08, 39.04, 66.31,
102.60, 102.80, 118.40, 119.66, 120.21, 122.32, 127.44, 133.66,
134.72, 143.47, 147.00, 148.82, 165.76, 167.85.
= 1.00 [d, 6 H, J = 6.2 Hz,
Acknowledgment
We thank supporting from FONDECYT 2010029 and FONDECYT
8000016
Anal. Calcd for C21H26O5N2: C, 65.27; H, 6.78; N, 7.25. Found: C,
63.63; H, 7.03; N, 6.75.
References
(1) Drugs Future 1988, 13, 207.
4-(4-Nitrosophenyl)-2,6-dimethyl-3,5-diethoxycarbonyl-1,4-di-
hydropyridine
Yield: 35%; mp 87–88 ºC.
(2) Hantzsch, A. Justus Liebigs Ann. Chem. 1882, 1, 215.
(3) Stout, D.; Meyers, A. Chem. Rev. 1982, 82, 223.
(4) Hilgeroth, A.; Billich, A.; Lilie, H. E. J. Med. Chem. 2001,
36, 367.
(5) Bhavik, B.; Dinesh, D.; Yogesh, Y.; Anamik, A.; Anil, A. K.
Bioorg. Med. Chem. 2001, 9, 1993.
(6) Yamada, S.; Misono, T.; Ichikawa, M.; Morita, C.
Tetrahedron 2001, 57, 8939.
(7) Jhy-Chong, J. C.; Jwu-Lai, J. L.; Chia-Sui, C. S.; Shwu-Fen,
S. F.; Chie-Ho, C. H.; Ing-Jun, I. J. Bioorg. Med. Chem.
2002, 10, 719.
IR (KBr): 3342, 2998, 1672, 1487, 1369, 1303, 1217, 1120, 1020,
810 cm–1.
1H NMR: = 1.21 (t, 6 H, J = 7.1 Hz, CH2CH3), 2.36 (s, 6 H,
RCH3), 4.10 (q, 4 H, J = 7.1 Hz, CH2CH3), 5.10 (s, 1 H, RCH), 5.70
(s, 1 H, NH), 7.50 (d, 2 H, J = 8.3 Hz, ArH), 7.70 (d, 2 H, J = 8.3
Hz, ArH).
13C NMR (75 MHz, CDCl3): = 14.24 (2 C), 19.66, 21.44, 40.44,
59.98 (2 C), 103.10, 121.11, 125.29, 128.21, 128.86, 129.03,
144.59, 155.74 (2 C), 165.63, 167.10.
(8) Rampa, A.; Chiarine, A.; Bisi, A.; Budriese, R.; Valenti, P.
Drug. Res. 1991, 41, 705.
(9) Squella, J. A.; Huerta, M.; Bollo, S.; Pessoa, H.; Núñez-
Vergara, L. J. Electrochimica Acta. 1997, 42, 2305.
(10) Díaz-Araya, G.; Godoy, L.; Naranjo, L.; Squella, J. A.;
Letelier, M. E.; Núñez-Vergara, L. J. Gen. Pharmacol. 1998,
31, 385.
Anal. Calcd for C19H22O5N2: C, 63.68; H, 6.19; N, 7.82. Found C,
66.20; H, 6.55; N, 6.96.
4-(4-Nitrosophenyl)-2,6-dimethyl-3,5-diisopropyloxycarbonyl-
1,4-dihydropyridine
(11) Núñez-Vergara, L. J.; Díaz-Araya, G.; Olea-Azar, C.; Atria,
A. M.; Bollo-Dragnic, S.; Squella, J. A. Pharm. Res. 1998,
15, 1690.
(12) Núñez-Vergara, L. J.; Navarrete-Encina, P. A.; Ortiz, M. E.;
Bollo, S.; Squella, J. A. Chem. Biol. Int. 1996, 101, 89.
(13) Núñez-Vergara, L. J.; Guíñez-Castro, J. E.; Bollo, S.;
Squella, J. A. Bol. Soc. Chil. Quím. 1996, 41, 363.
(14) Núñez-Vergara, L. J.; Ortiz, M. E.; Bollo, S.; Squella, J. A.
Chem. Biol. Int. 1997, 106, 1.
Yield: 40%; mp 101 ºC.
IR (KBr): 3309, 2982, 1700, 1649, 1489, 1345, 1301, 1218, 1104,
1016, 833 cm–1.
1H NMR (300 MHz, CDCl3):
CH(CH3)2], 1.26 [d, 6 H, J = 6.2 Hz, CH(CH3)2], 2.35 (s, 6 H,
RCH3), 4.96 [sept, 2 H, J = 6.2 Hz, CH(CH3)2], 5.07 (s, 1 H, CH),
5.85 (s, 1 H, RNH), 7.48 (d, 2 H, J = 8.8 Hz, ArH), 8.11 (d, 2 H,
J = 8.8 Hz, ArH).
= 1.11 [d, 6 H, J = 6.2 Hz,
13C NMR (75 MHz, CDCl3): = 19.69, 21.87, 21.12, 40.29, 67.40,
103.27, 103.42, 121.06, 123.19, 128.24, 129.10, 144.45, 146.14,
155.34, 165.66, 166.64, 166.70.
(15) Núñez-Vergara, L. J.; Bollo-Dragnic, S.; Olea-Azar, C.;
Santander, P.; Gunckel, S.; Squella, J. A. Bol. Soc. Chil.
Quím. 1998, 43, 231.
(16) Núñez-Vergara, L. J.; Sturm, J. C.; Olea-Azar, C.;
Navarrete-Encina, P.; Bollo, S.; Squella, J. A. Free Radical
Res. 2000, 32, 399.
Anal. Calcd for C21H26O5N2: C, 65.27; H, 6.78; N, 7.25. Found: C,
66.87; H, 6.96; N, 6.99.
(17) Núñez-Vergara, L. J.; Squella, J. A.; Bollo-Dragnic, S.;
Morello, A.; Repetto, Y.; Aldunate, J.; Letelier, M. Comp.
Biochem. Physiol., Part C: Toxicol. Pharmacol. 1997, 118,
105.
(18) Núñez-Vergara, L. J.; Squella, J. A.; Bollo-Dragnic, S.;
Marín-Catalán, R.; Pino, L.; Díaz, G.; Letelier, M. E. Gen.
Pharmacol. 1998, 30, 85.
4-(4-Nitrosophenyl)-2,6-dimethyl-3,5-dimethoxycarbonyl-1,4-
dihydropyridine
The procedure is almost the same as the described general proce-
dure with the following modification. The ethanolic solution of hy-
droxylamine formed was evaporated to dryness, and the crude
compound was dissolved in acetone. This solution was then poured
in the aq solution of FeCl3 followed by the rest of the workup.
Synthesis 2003, No. 18, 2781–2784 © Thieme Stuttgart · New York