Synthesis of 1, 4-Dihydropyridine Derivatives using Fe [(L)proline]₂ as Catalyst

Introduction

Chemical dihdropyridins reported by arthur hantzsch from 1882 years, he compounded _ᵝ-ketoester, aldehyde and ammohia that lead to forms of 1¡4-dihidropyridines where as reported   many advantages of 1¡4-dihydropiridin ,and  at  this time identify as importance and vital in treatment of calcium antagonists¹, antitumours², antidiabetics³, antagonists⁴ and antivirals⁵. Recently a number of articles have published on the synthesis of 1, 4-dihydropyridines^6-12. Heterogeneous catalysts have gained and have been widely used as a stable and an efficient catalyst for synthesis of organic compound.

We have synthesized of DHPs from ethyl acetoacetate, benzaldehyde, and ammonium acetate using Fe [(L)proline]₂ as catalyst (Scheme 1). Once the reaction goes to completion, the catalyst can be filtered, washed with warm ethanol, and reused without decrease in activity.

Previously, we have synthesized a number of heterocyclic compounds^13-18. Although numerous methods are capable of affecting these synthesis has been previously reported. Zn [(L)proline]₂  has been used previously as a catalyst for synthesis of organic compound¹⁹.

The  comparison  of  IR  spectra  shows   That   in  IR  L- prolin  spectra  seeing   NH  And  OH  spectra . and  was  deleted  Thes  spectra  in  Fe [ L- proline ]2  Catalysors , and  shows The  Complex was formed  between  Fe  and  L – prolin , and  in  fact  complex  is  similar  To  Zn [L- proline]2.

Therefore, we reported the development of an efficient, a facile method and green synthesis for 1, 4-DHPs by Fe [(L)proline]₂ as catalyst (Scheme 1). There is Fe [(L)proline]₂ as the catalyst were environmentally friendly, and easy separation.

Scheme 1 Click here to View scheme

General Procedure for the Preparation of the Fe [(L)proline]₂

A mixture of Triethylamine (1 ml) and L-proline (4 mmol) in methanol (10 ml) was added. After solubilization with heat, reaction mixture was stirred for 10 min and ferrous sulfate (2 mmol) was added. A white precipitate was readily formed and after 1 hour it was collected by filtration to give the desired complex. IR spectra confirm formation of Fe [(L)proline]_2, IR spectra fig 1 is for L-proline, IR spectra fig 2 is for ferrous sulfate and IR spectra fig 3 is for Fe [(L)proline]₂. Comparison of the spectra shows that loss some of signals and picks is sign for formation complex of Fe [(L)proline]₂.

Figure 1 Click here to View figure

Figure  2 Click here to View figure

Figure  3  Click here to View figure

General Procedure for the Preparation of diethyl 2, 6-dimethyl-4-phenylpyridine-3, 5-dicarboxylate

A mixture of ethyl acetoacetate (2 mol), benzaldehyde (1 mol) and ammonium acetate (1 mol) and Fe [(L)proline]₂ (% 10) in ethanol (20 ml was refluxed for 1.5 h. The obtained solid was filtered; the solid was washed with water and recrystallized using absolute ethanol.

Spectral data for diethyl 2, 6-dimethyl-4-phenylpyridine-3, 5-dicarboxylate

Yellow crystals, Yield 91%, IR (KBr, cm^-1) ν: 3405, 3012, 2955, 1728. ¹H NMR (400MHz, CDCl₃) δ: 1.25 (t, 6H, 2CH₃, J = 7. 4 Hz), 2.55 (s, 6H, 2CH₃), 4.45 (q, 4H, 2CH₂O, J = 7.4 Hz), 5.11 (s, 1H, CH), 7.23-7.80(m, 5H, H_arom) 8.88 (s, 1H, NH).

Acknowledgement

We gratefully acknowledge the financial support from the Research Council of Tonekabon Branch Islamic Azad University.

References

1. Visentin S., Rolando B., Di Stilo A., Frutterro R., Novara M., Carbone E., Roussel C., Vanthuyne N. and A. Gasco, J. Med. Chem., 47: 2688 (2004).
2. Tsuruo T., Iida H., Nojiri M., Tsukagoshi S. and Sakurai Y., Cancer Res., 43: 2905 (1983).
3.  Malaise W.J. and Mathias P.C.F., Diabetologia., 28: 153 (1985).
4.  Poindexter G.S., Bruce M.A., Breitenbucher J.G., Higgins M.A., Sit S.Y., Romine J.L., Martin S.W., Ward S.A., McGovern R.T., Clarke W., Russell J. and Antal-Zimanyi I., Bioorg. Med. Chem., 12: 507 (2004).
5. Krauze A., Germane S., Eberlins O., Sturms I. and Klusa V., Duburs G., Eur. J. Med. Chem., 34: 301 (1999).
6. Koukabi N., Kolvari E., Khazaei A., Zolfigol M.A., Shirmardi-Shaghasemi B., and Khavasi H.R., Chem. Commun., 47: 9230 (2011).
7. Ladani N.K., Mungra D.C., Patel M.P., and Patel R.G., Chin. Chem. Lett., 22: 1407 (2011).
8. Saini A., Kumar S., and Sandhu J.S., J. Sci. Ind. Res., 67: 95 (2008).
9. Bhatti R.S., Krishan P., Suresh, and Sandhu, J.S., J. Indian Chem. Soc., 87: 707 (2010).
10. Vijesh A.M., Isloor A.M., Peethambar S.K., Shivananda K.N., Arulmoli T., and Isloor, N.A., Eur. J. Med. Chem., 46: 5591 (2011).
11. Kolvari E., Zolfigol M.A., Koukabi N., and Shirmardi-Shaghasemi B., Chem. Papers., 65: 898 (2011).
12. Long, S., Panunzio, M., Petroli, A., Qin, W., and Xia Z., Synthesis., 7: 1071 (2011).
13. Azizian J., Hatamjafari F., Karimi A. R. and Shaabanzadeh M., Synthesis. 5: 765 (2006).
14. Azizian J., Shaabanzadeh M., Hatamjafari F. and Mohammadizadeh M.R., Arkivoc., (xi): 47 (2006).
15. Hatamjafari F., Synthetic Communications., ý 36: 3563  (2006).
16. Azizian J., Hatamjafari F. and Karimi A. R., Journal of Heterocyclic Chemistry.ý, 43: 1349 (2006).
17. Hatamjafari F. and Montazeri N., Turkish Journal of Chemistry.ý, 33: 797 (2009).
18. Hatamjafari F., Orient. J. Chem., 28: 141 (2012).
19. Rajender Reddya K., Rajasekhara C. V., and Gopi G., Synthetic Communications.,ý 37: 1971 (2007).

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