Organic Process Research & Development 2003, 7, 95−97
Nitration of Phenol and Substituted Phenols with Dilute Nitric Acid Using
Phase-Transfer Catalysts
Ashutosh V. Joshi, Mubeen Baidoosi, Sudip Mukhopadhyay,† and Yoel Sasson*
Casali Institute of Applied Chemistry, Hebrew UniVersity of Jerusalem, Jerusalem 91904, Israel
Abstract:
utilized by many investigators. Catalytic nitration of aromatic
hydrocarbons with concentrated nitric acid in the presence
of solid acids8 has received attention with regards to the
regioselectivity. In some cases, the reaction has been
performed in expensive media such as ionic liquids9 and
microemulsions.10 A sophisticated technique, microwave-
assisted nitration of aromatic hydrocarbons with dilute nitric
acid, has also been studied recently.11 With regards to
nitration of phenols, concentrated nitric acid or mixed acids
are promising; their use is always associated with the
formation of dinitro compounds, oxidized products, and
unspecified resinous tarry materials resulting from the over-
oxidation of the substrate. Noteworthy, the typical yield of
direct nitration never exceeds 60%2 because of the above-
mentioned side reactions in most of the cases, making these
existing processes uneconomical. Therefore, it is worthwhile
to consider an alternative highly selective nitration process
scheme by using a mild nitrating agent such as dilute nitric
acid. Thus, in this work, we will report results of the selective
nitration of phenols with 6 wt % nitric acid in the presence
of a phase-transfer catalyst, namely, tetrabutylammonium
bromide (TBAB).
Highly selective nitration of phenol and substituted phenols to
the corresponding nitro compounds is accomplished under mild
conditions in a liquid-liquid two-phase system with dilute nitric
acid (6 wt %) and in the presence of a phase-transfer catalyst.
The consequence of various phase-transfer catalysts on the
reaction rate is contemplated. Tetrabutylammonium bromide
(TBAB) was found to be the most effective phase-transfer
catalyst in terms of conversion and selectivity. The experimental
results are accounted for by a binary role of the phase-transfer
catalyst in this system. It is anticipated to extract nitric acid
into the organic phase via the hydrogen-bonded complex and
to supply HBr, formed in situ in the reaction scheme by anion
exchange, which is believed to be the key for generation of the
active nitration species, nitronium ion in the organic phase.
Introduction
Nitration of aromatic compounds is an industrially
consequential reaction1 as the nitrated products are important
intermediates for fine chemicals and pharmaceuticals. Usu-
ally, nitration reactions are not selective and are the cause
of environmental concerns regarding the disposal of the large
excess of mixed acids employed in these processes. Thus,
the utility of this processes2,3 are generally low. Besides
mixed acids, several other nitrating agents, including con-
centrated nitric acid, acid anhydrides or triflates,4 peroxy
nitrite,5 metal nitrates,6 and nitrogen oxides,7 have been
Results and Discussion
Conversions for various phenolic compounds are shown
in Table 1. In case of unsubstituted phenol the selectivity
was less. This is due to the oxidation of phenol to 1,4-
benzoquinone (10%). A 90% yield of mononitrophenol was
concurrently obtained (ortho/para ratio was 6:4). In the
absence of TBAB only traces of nitrophenol were detected
under the above reaction conditions. Noteworthy, when para-
substituted phenols were used, the nitration occurred at the
† Present address: Chemical Engineering Department, University of California
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10.1021/op0200120 CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/11/2002
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