Substrate Directed Regioselective Monobromination of Aralkyl Ketones Using N-Bromosuccinimide Catalysed by Active Aluminium Oxide: α-Bromination versus Ring Bromination
Bromination of aralkyl ketones using N-bromosuccinimide in presence of active Al2O3 provided either α-monobrominated products in methanol at reflux or mononuclear brominated products in acetonitrile at reflux temperature with excellent isolated yields depending on the nature of substrate employed. The α-bromination was an exclusive process when aralkyl ketones containing moderate activating/deactivating groups were subjected to bromination under acidic Al2O3 conditions in methanol at reflux while nuclear functionalization was predominant when aralkyl ketones containing high activating groups were utilized for bromination in presence of neutral Al2O3 conditions in acetonitrile at reflux temperature. In addition, easy isolation of products, use of inexpensive catalyst, short reaction time (10–20？min), and safe operational practice are the major benefits in the present protocol. 1. Introduction Nowadays, researchers are focusing on the development of more acceptable bromination protocols to accomplish increasing demands for “organohalogen” chemistry and to achieve higher efficiency and selectivity of the bromination reactions which include α-bromination and nuclear bromination. The resulting α-brominated or nuclear brominated products acquired wide range of utility in organic synthesis [1–3]. Nuclear brominated ketones are found to be useful intermediates in C–C coupling reactions, as precursors to organometallic species and in nucleophilic substitutions. It is well known that use of molecular bromine [4] as a basic electrophilic brominating reagent has several drawbacks. Alternative reagents were reported in the literature, for example, cupric bromide [5], dioxane dibromide [6], tetrabutyl ammonium tribromide [7], H2O2-HBr [8], bromodimethyl sulfoniumbromide [9], ethylene bis(N-methyl imidazolium) ditribromide [10], trihaloisocyanuric acids [11], pyridinium bromochromate [12], and NH4Br-oxone [13]. In addition, a popular and superior brominating agent such as N-bromosuccinimide [14] was utilized for α-bromination of carbonyl compounds using a radical initiator such as azobisisobutyronitrile (AIBN) or dibenzoyl peroxide (BPO) [15] and, later, it has been demonstrated that the reactivity of NBS could be modulated with ionic liquids [16], photochemical energy [17]; sonochemical energy [18], solvent free reaction conditions (SFRC) [19] and various catalysts such as Mg(ClO4)2 [20], NH4OAc [21], amberlyst-15 [22], silica supported NaHCO3 [23], sulfonic acid functionalized silica [24], FeCl3 [25], montmorillonite-K10 [26], and Silica gel [27]. NBS also is
References
[1]
R. C. Larock, Comprehensive Organic Transformations, Wiley-VCH, New York, NY, USA, 2nd edition, 1999.
[2]
A. W. Erian, S. M. Sherif, and H. M. Gaber, “The chemistry of α-haloketones and their utility in heterocyclic synthesis,” Molecules, vol. 8, no. 11, pp. 793–865, 2003.
[3]
C. Christophersen, “Secondary metabolites from marine bryozoans. A review,” Acta Chemica Scandinavica B, vol. 39, no. 7, pp. 517–529, 1985.
[4]
M. B. Smith and J. March, Advanced Organic Chemistry, Reactions, Mechanisms and Structure, John Wiley & Sons, New Jersey, NJ, USA, 6th edition, 2006.
[5]
L. C. King and G. K. Ostrum, “Selective bromination with copper(II) bromide,” Journal of Organic Chemistry, vol. 29, no. 12, pp. 3459–3461, 1964.
[6]
S. J. Pasaribu and L. K. Williams, “Selective bromination of substituted acetophenones with dioxan dibromide,” Australian Journal of Chemistry, vol. 26, no. 6, pp. 1327–1331, 1973.
[7]
S. Kajigaeshi, T. Kakinami, T. Okamoto, and S. Fujisaki, “Synthesis of bromoacetyl derivatives by use of Tetrabutylammonium Tribromide,” Bulletin of the Chemical Society of Japan, vol. 60, no. 3, pp. 1159–1160, 1987.
[8]
J. Ju, Y. J. Li, J. R. Gao et al., “High selectively oxidative bromination of toluene derivatives by the H2O2-HBr system,” Chinese Chemical Letters, vol. 22, no. 4, pp. 382–384, 2011.
[9]
A. T. Khan, M. A. Ali, P. Goswami, and L. H. Choudhury, “A mild and regioselective method for α-bromination of β-keto esters and 1,3-diketones using bromodimethylsulfonium bromide (BDMS),” Journal of Organic Chemistry, vol. 71, no. 23, pp. 8961–8963, 2006.
[10]
R. Hosseinzadeh, M. Tajbakhsh, M. Mohadjerani, and Z. Lasemi, “Ethylenebis(N-methylimidazolium) ditribromide (EBMIDTB): an efficient reagent for the monobromination of 1,3-diketones and β-ketoesters,” Monatshefte fur Chemie, vol. 140, no. 1, pp. 57–60, 2009.
[11]
G. F. Mendon？a, H. C. Sindra, L. S. de Almeida, P. M. Esteves, and M. C. S. de Mattos, “Trihaloisocyanuric acids as convenient reagents for regioselective halogenation of β-dicarbonyl compounds,” Tetrahedron Letters, vol. 50, no. 4, pp. 473–475, 2009.
[12]
Y. Sarrafi, M. Sadatshahabi, and K. Alimohammadi, “A mild, simple and efficient method for selective α-monobromination of 1,3-diketones and β-keto-esters using pyridinium bromochromate,” Chinese Chemical Letters, vol. 20, no. 4, pp. 393–396, 2009.
[13]
A. K. MacHarla, R. C. Nappunni, M. R. Marri, S. Peraka, and N. Nama, “Oxidative bromination of ketones using ammonium bromide and oxone,” Tetrahedron Letters, vol. 53, no. 2, pp. 191–195, 2012.
[14]
K. Tanemura, T. Suzuki, Y. Nishida, K. Satsumabayashi, and T. Horaguchi, “Halogenation of aromatic compounds by N-chloro-, N-bromo- and N-iodosuccinimide,” Chemistry Letters, vol. 32, no. 10, pp. 932–933, 2003.
[15]
H. Schmid and P. Karrer, “Verbesserung und Erweiterung der Bromierungsmethode mit Brom-succinimid,” Helvetica Chimica Acta, vol. 29, no. 3, pp. 573–581, 1946.
[16]
H. M. Meshram, P. N. Reddy, P. Vishnu, K. Sadashiv, and J. S. Yadav, “A green approach for efficient α-halogenation of β-dicarbonyl compounds and cyclic ketones using N-halosuccinimides in ionic liquids,” Tetrahedron Letters, vol. 47, no. 6, pp. 991–995, 2006.
[17]
S. S. Arbuj, S. B. Waghmode, and A. V. Ramaswamy, “Photochemical α-bromination of ketones using N-bromosuccinimide: a simple, mild and efficient method,” Tetrahedron Letters, vol. 48, no. 8, pp. 1411–1415, 2007.
[18]
M. V. Adhikari and S. D. Samant, “Sonochemical bromination of acetophenones using p-toluenesulfonic acid-N-bromosuccinimide,” Ultrasonics Sonochemistry, vol. 9, no. 2, pp. 107–111, 2002.
[19]
I. Pravst, M. Zupan, and S. Stavber, “Halogenation of ketones with N-halosuccinimides under solvent-free reaction conditions,” Tetrahedron, vol. 64, no. 22, pp. 5191–5199, 2008.
[20]
D. Yang, Y. L. Yan, and B. Lui, “Mild α-halogenation reactions of 1,3-dicarbonyl compounds catalyzed by Lewis acids,” Journal of Organic Chemistry, vol. 67, no. 21, pp. 7429–7431, 2002.
[21]
K. Tanemura, T. Suzuki, Y. Nishida, K. Satsumabayashi, and T. Horaguchi, “A mild and efficient procedure for α-bromination of ketones using N-bromosuccinimide catalysed by ammonium acetate,” Chemical Communications, vol. 10, no. 4, pp. 470–471, 2004.
[22]
H. M. Meshram, P. N. Reddy, K. Sadashiv, and J. S. Yadav, “Amberlyst-15-promoted efficient 2-halogenation of 1,3-keto-esters and cyclic ketones using N-halosuccinimides,” Tetrahedron Letters, vol. 46, no. 4, pp. 623–626, 2005.
[23]
A. Rahman and S. B. Jonnalagadda, “Simple and efficient system for the α-bromination of a β-ketoester by using N-bromosuccinimide in the presence of silicasupported NaHCo3 as the heterogeneous catalyst: an environmentally benevolent approach,” Synthetic Communications, vol. 42, no. 8, pp. 1091–1100, 2012.
[24]
B. Das, K. Venkateswarlu, G. Mahender, and I. Mahender, “A simple and efficient method for α-bromination of carbonyl compounds using N-bromosuccinimide in the presence of silica-supported sodium hydrogen sulfate as a heterogeneous catalyst,” Tetrahedron Letters, vol. 46, no. 17, pp. 3041–3044, 2005.
[25]
H. Jin, Z. D. Huang, C. X. Kuang, and X. K. Wang, “Iron-catalyzed bromination of aryl azides by N-bromosuccinimide: efficient method for the synthesis of brominated aryl azides,” Chinese Chemical Letters, vol. 22, no. 3, pp. 310–313, 2011.
[26]
R. B. Mohan and N. C. Gangi Reddy, “Regioselective α-bromination of aralkylketones using N-bromosuccinimide in presence of montmorillonite k-10 clay: a simple and efficient method,” Synthetic Communications, vol. 43, no. 19, pp. 2603–2614, 2013.
[27]
R. B. Mohan, V. V. Ramana Kumar, N. C. Gangi Reddy, and S. Mahender Rao, “Silica gel catalyzed α-bromination of ketones using N-bromosuccinimide: an easy and rapid method,” Chinese Chemical Letters, vol. 25, no. 1, pp. 179–182, 2014.
[28]
J. Duan, L. H. Zhang, and W. R. Dolbier Jr., “A convenient new method for the bromination of deactivated aromatic compounds,” Synlett, no. 8, pp. 1245–1246, 1999.
[29]
P. Bovonsombat and E. McNelis, “Ring halogenations of polyalkylbenzenes with N-halosuccinimide and acidic catalysts,” Synthesis, no. 2, pp. 237–241, 1993.
[30]
J. Auerbach, S. A. Weissman, T. J. Blacklock, M. R. Angeles, and K. Hoogsteen, “N-bromosuccinimide/dibromodimethylhydantoin in aqueous base: a practical method for the bromination of activated benzoic acids,” Tetrahedron Letters, vol. 34, no. 6, pp. 931–934, 1993.
[31]
Y. Goldberg and H. Alper, “Electrophilic halogenation of aromatics and heteroaromatics with N-halosuccinimides in a solid/liquid system using an H+ ion exchanger or ultrasonic irradiation,” Journal of Molecular Catalysis, vol. 88, no. 3, pp. 377–383, 1994.
[32]
V. Paul, A. Sudalai, T. Daniel, and K. V. Srinivasan, “Regioselective bromination of activated aromatic substrates with N-bromosuccinimide over HZSM-5,” Tetrahedron Letters, vol. 35, no. 38, pp. 7055–7056, 1994.
[33]
K. Smith, Solids Supports and Catalysts in Organic Synthesis, Ellis Horwood, Chichester, UK, 1992.
[34]
P. Laszlo, Preparative Chemistry Using Supported Reagents, Academic Press, London, UK, 1987.
[35]
H. van Bekkum, E. M. Flanigen, and J. C. Jansen, Introduction to Zeolite Science and Practice, vol. 58 of Studies in Surface Science and Catalysis, 1991.
[36]
H. Pines and W. O. Haag, “Alumina: catalyst and support. I: alumina, its intrinsic acidity and catalytic activity,” Journal of the American Chemical Society, vol. 82, no. 10, pp. 2471–2483, 1960.
[37]
R. J. Farrauto, K. E. Voss, and R. M. Heck, “Ceria-alumina oxidation catalyst,” US Patent 5462907, 1995.
[38]
A. Corado, A. Kiss, H. Kn？zinger, and H. D. Müller, “Catalytic isomerization of olefins on alumina. II: catalyst deactivation and its effects on the mechanism,” Journal of Catalysis, vol. 37, no. 1, pp. 68–80, 1975.
[39]
A. Tsuruoka, Y. Kaku, H. Kakinuma et al., “Synthesis and antifungal activity of novel thiazole-containing triazole antifungals. II: optically active ER-30346 and its derivatives,” Chemical and Pharmaceutical Bulletin, vol. 46, no. 4, pp. 623–630, 1998.
