Molbank 2006, M471

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Diethyl 2,6-Dimethyl,4-(1,1,1-trichloromethyl)-1,4-dihydropyridine-3,5-dicarboxylate

Fatma Aydin^a* and Recep Ozen^b

^aCanakkale Onsekiz Mart University, Department of Chemistry, 17020 Canakkale TURKEY

^bMersin University, Department of Chemistry, 33342 Mersin TURKEY

Tel: +90 286 2180018-1862, Fax: +90 286 2180533 e-mail: [email protected]

*Author to whom correspondence should be addressed

Received: 12 October 2005 / Accepted: 24 October 2005 / Published: 28 February 2006

Keywords: Hantzsch reaction, 1,4-dihydropyridines, chloral, KF/Al₂O₃

In 1882, Hantzsch reported the first synthesis of dialkyl 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates from a refluxing mixture of an aldehyde, a β-ketoester, and aqueous ammonium hydroxide in ethanol.[1] 1,4-dihydropyridines (1,4-DHPs) are well known as Ca⁺² channel blockers.[2,3]

Concentric H₂SO₄ (5 mL) was dropped on chloral hydrate (3 g) and 1,1,1-trichloroacetaldehyde was distilled at 98^oC. Acetylacetone (4 mL, 40 mmol), freshly distilled 1,1,1-trichloroacetaldehyde (2.94 g, 20 mmol) and CH₃COONH₄ (1.44 g, 20 mmol) were dissolved in acetonitrile (15 mL). This mixture was added on [4] and refluxed for 3 h. The progress of the reaction was monitored by TLC analysis. After completion of the reaction, the resulting suspension was filtered and solid washed with acetonitrile (5 mL), solvent was evaporated. Residue was washed with water and extracted in CH₂Cl₂ (3x5 mL). The solution of CH₂Cl₂ was dried over anhydrous Na₂SO₄ and then filtered._. The solvent was removed under reduced pressure and pale yellow oil product in a good yield, 67.1 % (4.97 g).

UV λ_max (nm; ethyl alcohol) / ε (dm³.mol^-1.cm^-1): 392 / 6270

IR (KBr) (υ cm^-1): 3419 (N-H); 2984 (C=C); 1722 (C=C-C=O); 1031 (C-O); 818 (C-Cl).

¹H-NMR (400 MHz, CDCl₃): δ= 1.21 (t, 6H, -CH₃); 2.16 (s, 6H, -CH₃); 3.31 (s, 1H); 4.12 (q, 4H, methylenic).

¹³C-NMR (100 MHz, CDCl₃): δ= 29.8, 31.6, 58.5, 62.0, 81.7, 166.7, 169.0, 199.5.

Elemental Analysis: Calculated for C₁₄H₁₈ Cl₃NO₄: C, 45.37%; H, 4.89%; Cl, 28.69%; N, 3.78%. Found: C, 45.21%; H, 4.84%; Cl, 28.72%; N, 3.82%.

References

1. A. Hantzsch, Ann. 215, 1, 72 (1882); Ber. 18 1744 (1885); 19, 289 (1886).

2. a) Bossert, F.; Meyer, H.; Wehinger, E. Angew. Chem., Int. Ed. Engl. 1981, 20, 762-769;

b) Nakayama, H.; Kasoaka, Y. Heterocycles 1996, 42, 901-909.

3. Love, B.; Goodman, M.; Snader, K.; Tedeschi, R.; Macko, E. J. Med. Chem. 1974, 17, 956-965.

4. Aydin, F. and Ozen, R. J. Chem. Res-S, (7), 2004, 486-487.

5. Younessi, A. and Krapivin, G. D., Molbank, 2003, M344

Sample Availability: Available from MDPI.

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