Brominated aromatic compounds are valuable intermediates in organic synthesis and they have been used widely in industrially important products and biologically active substrates as antitumor, antifungal, antibacterial, antineoplastic and antviral compounds. The need for isomerically pure bromoaromatics has led to investigations into more selective brominating agents and several methods have been reported in the literatures. Reactions making use of organic ammonium tribromides (OATB) like tetrabutylammonium tribromide (TBATB), 1,8-diazabicyclo[5.4.0]-tetrabutylammoniumtribromide, pyridine hydrobromide perbromide, methods employing anodic brominations in organic solvents, and bromine trifluoride have been fully investigated. Various methods of oxidative nuclear bromination of aromatic molecules have been developed including KBr-H2O2 using metal-oxo catalysts, KBr-NaBO3·4H2O, BuOBr-zeolite, LiBr-(NH4)2Ce(NO3)6, and Oxone-NaBr. Quite recently, Firouzabadi and the coworkers have reported heteropoly acid cesium salt/cetyltrimethylammonium bromide as a catalytic heterogeneous system which highly controls regioselective bromination of aromatic compounds with bromine. Some of these protocols suffer from harsh reaction conditions or cumbersome extraction procedures. Therefore milder and environmentally less toxic methods are desirable. Following our continued interest in the development of mild and regioselective halogenating reagents, herein we report synthesis and application of γ-picolinium bromochromate (γ-PBC) as a mild, efficient and highly regioselective oxidative mono-brominating reagent for the bromination of aromatic compounds. The reagent was conveniently prepared by the reaction of equimolar quantities of chromium trioxide, 47% aqueous hydrobromic acid and γ-picoline in 88% yield (m.p. 285 C, decomposed)). γ-PBC is a dark brown solid, non-hygroscopic, air-stable and moderately light sensitive, which should be protected from the light during preparation and storage. The reagent is insoluble in THF, Et2O, benzene, toluene, nitrobenzene, ethyl acetate and acetone, sparingly soluble in CHCl3 and H2O, soluble in DMF, DMSO. The pH value for 0.01 M water solution of γPBC is 3.37, and this value is higher than pyridinium chlorochromate (1.75), pyridinium bromochromate (3.35 for 0.03 M aq. solution) and lower than quinolinium bromchromate (QBC) (3.87). The structure of the reagent (1) was confirmed by elemental analysis, H NMR and IR (KBr) which clearly showed Cr=O stretching vibrations at 1040, 955 and 760 which is comparable with the related bands in QBC. The brominating potential of this reagent in regioselective bromination of aromatic compounds in glacial acetic acid at 90 C was investigated (Table 1). Our results indicate that γPBC monobrominate the active aromatic compounds in an oxidative bromination reacton conveniently. In this study the regent is para-selective and no trace of other regioisomers and dibromo products could be detected. However, acetophenone as aromatic substrate with electron withdrawing group gave a mixture of regio-isomers (meta/para ratio 3 : 1 by H NMR) and highly deactivated aromatic compounds such as nitrobenzene entirely resist the bromination reaction. Bromination of acetanilide was also conducted by γ-PBC in glacial acetic acid under microwave (MW) irradiation which provided para-bromoacetanlide in 85% yield. The reaction under MW was also para-selective and showed a considerable rate enhancement (Table 1) in comparison to thermal condition. Full investigation of application of this methodology to the bromination of aromatic substrates is in progress. In conclusion, we have found γ-picolinium bromochromate as an easily accessible, mild, efficient and regioselective brominating reagent, which afforded the corresponding bromoorganics in good yields.
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Jan 1, 2004
Fernando Gómez-Contreras + 6
Open Access
