Catalyst Free Synthesis of Pyridine-2,6-bis(2-bromo-propane-1,3-dione) and Pyrdine-2,6-bis(N-arylthiazoline-2-thiones)

Korany A. Ali^1*, Mohamed A. Elsayed¹, Eman Ali Ragab²

¹Applied Organic Chemistry Department, National Research Centre, Dokki-Giza, Egypt.
²Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.

DOI: 10.4236/gsc.2015.51006                

Abstract

We have described herein a catalyst-free preparation method of pyridine-2,6-bis(N-alkylthiazoline-2-thiones) (4a-i) by the reaction of primary amines, CS₂, and pyridine-2,6-bis(2-bromo-1,3- dicarbonyl) derivatives (2a-c) in water. Also, we have described a catalyst free, green chemistry protocols to monobromination of pyridine-2,6-bis(2-bromo-1,3-dicarbonyl) derivatives with high yield, using NBS as a brominating agent, that led to eco-friendly isolation and purification proce-dures. Furthermore, we have studied the reactivity of pyridine-2,6-bis(2-bromo-1-methyl-pro- pane-1,3-dione) (2a) towards thiourea to afford 2,6-bis(5-benzoyl-2-aminothiazol-4-yl)pyridine (9).

Keywords

N-Alkylthiazoline-2-Thiones, Catalyst-Free Reactions, Monobromination, 2, 6-Disubstituted Pyridine

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Kaye, P.T., Meakins, G.D., Smith, A.K. and Tirel, M.D. (1983) N,N-Disubstituted 2-Aminothiazole-5-carboxylates: Preparation and Rotation of Functional Groups. Journal of the Chemical Society, Perkin Transactions, 1, 1677-1680. http://dx.doi.org/10.1039/p19830001677
[2]	Yoshida, J., Yano, S., Ozawa, T. and Kawabata, N. (1984) Regioselective Synthesis of Dihydrofurans from 2,2- Dibromo-1,3-diketone and Olefin Using Copper. Tetrahedron Letters, 25, 2817-2820. http://dx.doi.org/10.1016/S0040-4039(01)81298-3
[3]	Salama, T.A. and Novak, Z. (2011) N-Halosuccinimide/SiCl4 as General, Mild and Efficient Systems for the α-Monohalogenation of Carbonyl Compounds and for Benzylic Halogenations. Tetrahedron Letters, 52, 4026-4029. http://dx.doi.org/10.1016/j.tetlet.2011.05.135
[4]	Ogilvie, W. and Rank, W. (1987) Thermolysis of Geminal Diazides: A Novel Route to 1,3,4-Oxadiazoles. Canadian Journal of Chemistry, 65, 166-169. http://dx.doi.org/10.1139/v87-025
[5]	Karimi, S., Grohmann, K.G. and Todaro, L. (1995) Intramolecular Ring-Opening of Cyclopropanones by Enolate Anions. The Journal of Organic Chemistry, 60, 554-559. http://dx.doi.org/10.1021/jo00108a016
[6]	Steven, J.C. and Harry, H.W. (1995) The Conversion of α-Bromo-β-Dicarbonyls to Vicinal Tricarbonyls Using Dimethyldioxirane and Base. Tetrahedron Letters, 36, 7735-7738. http://dx.doi.org/10.1016/0040-4039(95)01576-4
[7]	Garbisch, E.W. (1965) Cycloalk-2-Enones and α,β,α',β'-Cycloalkadienones. A. Synthesis. B. On the Direction of Bromination of 2-Substituted Cycloalkanones and Their Ketals. The Journal of Organic Chemistry, 30, 2109-2120. http://dx.doi.org/10.1021/jo01018a001
[8]	Teo, K.E. and Warnhoff, E.W. (1973) .Alpha.-Halo Ketones. VII. Origin of Disubstitution Products in Ketone Halogenation. New Mechanism. Journal of the American Chemical Society, 95, 2728-2729. http://dx.doi.org/10.1021/ja00789a077
[9]	Tanemura, K., Suzuki, T., Nishida, Y., Satsumabay, K. and Horaguchi, T. (2003) Halogenation of Aromatic Compounds by N-chloro-, N-bromo-, and N-iodosuccinimide. Chemistry Letters, 32, 932-933. http://dx.doi.org/10.1246/cl.2003.932
[10]	Toplak, R.B., Rocherulle, P. and Lorcy, D. (2002) Unexpected Reaction of Dimethoxycarbonyl Dithiole-2-Thione or Tetramethoxycarbonyl TTF as Dipolarophiles. Tetrahedron Letters, 43, 3879-3882. http://dx.doi.org/10.1016/S0040-4039(02)00672-X
[11]	Eid, S., Guerro, M. and Lorcy, D. (2006) 1,3-Thiazoline-2-thione-4,5-dithiolato, an Efficient Building Block towards Functionalized Dithiadiazafulvalenes. Tetrahedron Letters, 47, 8333-8336. http://dx.doi.org/10.1016/j.tetlet.2006.09.079
[12]	Murphy, G.J. and Holder, J.C. (2000) PPAR-γ Agonists: Therapeutic Role in Diabetes, Inflammation and Cancer. Trends in Pharmacological Sciences, 21, 469-474. http://dx.doi.org/10.1016/S0165-6147(00)01559-5
[13]	Lamon, R.W. and Humphlett, W.J. (1967) 4-Thiazoline-2-thiones. IV. Preparation from Amino Acids. Journal of Heterocyclic Chemistry, 4, 605-609. http://dx.doi.org/10.1002/jhet.5570040424
[14]	Ge, Z.-M., Li, Q., Zheng, S.-J., Cheng, T.-M., Cui, Y.-X. and Li, R.-T. (2006) Facile One-Pot Synthesis of Ethyl 3-Alkyl-4-hydroxy-2-thioxothiazolidine-4-carboxylates. Chinese Journal of Chemistry, 24, 381-385. http://dx.doi.org/10.1002/cjoc.200690073
[15]	Ali, K.A., Abdalghfar, H.S., Mahmoud, K. and Ragab, E.A. (2013) Synthesis and Antitumor Activity of New Poly-Substituted Thiophenes and 1,3,4-Thiadiazoles Incorporating 2,6-Pyridine Moieties. Journal of Heterocyclic Chemistry, 50, 1157-1164.
[16]	Ali, K.A., Abd-Elzaher, M.M. and Mahmoud, K. (2013) Synthesis and Anticancer Properties of Silver(I) Complexes Containing 2,6-Bis(substituted)pyridine Derivatives. International Journal of Medicinal Chemistry, 2013, Article ID: 256836. http://dx.doi.org/10.1155/2013/256836
[17]	Ali, K.A. (2012) Synthesis of Pyridine-2,6-bis((E)-2-benzylidine-3-oxopropanenitrile) and Its Behavior towards Nitrogen Binucleophiles. Heterocycles, 85, 1975-1986. http://dx.doi.org/10.3987/COM-12-12515
[18]	Farag, A.M., Elsayed, M.A. and Ali, K.A. (2012) Synthesis of Some New Pyridine-2,6-bis-heterocycles. Heterocycles, 85, 1913-1923. http://dx.doi.org/10.3987/COM-12-12483
[19]	Ghozlan, S.A.S., Al-Omar, M.A., Amr, A.E., Ali, K.A. and Abd El-Wahab, A.A. (2011) Synthesis and Antimicrobial Activity of Some Heterocyclic 2,6-Bis(substituted)-1,3,4-thiadiazolo-, Oxadiazolo and Oxathiazolidino-Pyridine Derivatives from 2,6-Pyridine Dicarboxylic Acid Dihydrazide. Journal of Heterocyclic Chemistry, 48, 1103-1110. http://dx.doi.org/10.1002/jhet.690
[20]	Ali, K.A., Elsayed, M.A. and Abdalghfar, H.S. (2011) Synthesis and Reactions of 2,6-Bis[3-oxo-3-propanenitrile- 2-(N,N-dimethylamino)methylene] pyridine. Arkivoc, ii, 103-114.
[21]	Ali, K.A. (2010) A New Convenient Synthesis of Some Novel 2,6-Disubstituted-Pyridine Derivatives. Arkivoc, xi, 55-63. http://dx.doi.org/10.3998/ark.5550190.0011.b06
[22]	Xi, Z., Liu, F., Zhou, Y. and Chen, W. (2008) CuI/L (L = Pyridine-Functionalized 1,3-Diketones) Catalyzed C–N Coupling Reactions of Aryl Halides with NH-Containing Heterocycles. Tetrahedron, 64, 4254-4259. http://dx.doi.org/10.1016/j.tet.2008.02.082