LETTER
1245
A Convenient New Method for the Bromination of Deactivated Aromatic
Compounds
Jianxin Duan, Lian Hao Zhang, William R. Dolbier, Jr.*
Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA
E-mail: wrd@chem.ufl.edu
Received 9 June 1999
Abstract: Treatment of deactivated aromatic compounds with N-
bromosuccinimide in trifluoroacetic acid solvent in the presence of
sulfuric acid gave the corresponding monobromoaromatic com-
pounds in good to excellent yields.
Key words: bromination, aromatic compounds
At this time we wish to report that use of trifluoroacetic
acid (TFA) as solvent, with NBS and catalytic H2SO4 as
the active source of electrophilic bromine, seems to be an
ideal medium for bromination of deactivated aromatic
compounds. For example, treatment of trifluoromethyl-
benzene with 1.5 equivalents of NBS in the presence of
H2SO4 in TFA at room temperature gave m-bromo(triflu-
oromethyl)-benzene in good yield, with the efficiency of
the reaction being dependent upon the concentration of
sulfuric acid, as shown in Table 1. Without sulfuric acid
the reaction does not occur, but if the ratio (V/V) of H2SO4
to TFA gets too high, (i.e., 0.4), hydrolysis of the trifluo-
romethyl group begins to be observed (Entry 4 of Table
1). Maintaining a ratio of 0.3 allows a good conversion,
with little, if any, benzoic acid being formed.
Bromoaromatics are highly useful synthetic intermedi-
ates, but ring bromination of strongly deactivated aromat-
ics continues to pose synthetic problems. Among the
reported methods for the bromination of deactivated aro-
matic compounds, many suffer from the use of hazardous
reagents or harsh reaction conditions.1,2 Thus, reagents
which utilize N-bromosuccinimide (NBS) or the analo-
gous 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) as
the source of electrophilic bromine have emerged as being
among the most useful for carrying out such difficult re-
actions.3-7
The first significant report was that of Lambert,4 who, in
a limited study, used NBS in an aqueous H2SO4 medium
to brominate nitrobenzene. In a much more thorough and
useful investigation, Eguchi used DBDMH with
CH3SO3H, CF3SO3H, or H2SO4 in CH2Cl2 or CHCl3 as
solvent to successfully brominate a number of electron-
deficient aromatics, including nitrobenzene, methyl ben-
zoate and trifluoromethylbenzene.5 However, more high-
ly deactivated aromatics than these, such as m-
dinitrobenzene, could not be brominated under such con-
ditions. Schlosser, with a specific interest in brominating
the highly unreactive 1,3-bis(trifluoromethyl)benzene,
found that DBDMH in concentrated H2SO4 or CF3SO3H
(without CH2Cl2 solvent) did that job nicely.6
Table 1 Effect of the ratio of H2SO4 to TFA (v/v) on the bromination
of (trifluoromethyl)benzene at 26 °C.
a by 19F NMR; b Benzoic acid was detected by 1H NMR
Brominations of other deactivated aromatics were found
to proceed with similar success, with the results being giv-
en in Table 2. Even the very strongly deactivated aromatic
compound, 1,3-dinitrobenzene, which was not able to be
brominated under Eguchi conditions,5 when subjected to
our reaction conditions at slightly higher temperature
(45 °C) for 48 h, gave the 5-brominated product in mod-
erate (45%) yield.8 As expected, relatively reactive aro-
matic compounds such as benzene reacted very rapidly
with NBS/TFA/H2SO4 at room temperature. The reaction
was complete in 2 h, giving bromobenzene in high yield
(91%).
Though all the reported methods based on NBS or DBD-
MH work well for the active and moderately deactivated
aromatic compounds, they can not be applied to very
strongly deactivated aromatic compounds, such as 1,3-
dinitrobenzene. Our goal was to find bromination condi-
tions that would be generally useful for deactivated ben-
zenes, but most specifically, would be useful for
brominating trifluoromethyl-substituted benzenes without
giving rise to significant hydrolysis.
In our study, trifluoroacetic acid was found to be the most
effective solvent of those examined, better than CH2Cl2,
CH3CO2H, or H2O, and it was the only one of this group
Synlett 1999, No. 8, 1245–1246 ISSN 0936-5214 © Thieme Stuttgart · New York