Organic Process Research & Development 2008, 12, 349–354
Highly Reactive and Regenerable Fluorinating Agent for Oxidative Fluorination of
Aromatics
Krishna Murthy Janmanchi and William R. Dolbier, Jr.*
Department of Chemistry, UniVersity of Florida, GainesVille, Florida 32611-7200
Abstract:
CsSO4F,7,13 various N-F8,14,15 and N+-F compounds,8,16,17 as well
as elemental F2 itself.5 However, with most of these compounds
requiring F2 for synthesis, they are all relatively expensive,
generally highly toxic, and often dangerous to use, thus
effectively precluding their use in commercial manufacture of
fluoroaromatics.
Alternatively, fluorides of transition metals have been
examined as fluorinating agents. Organic compounds, including
aromatic systems, have been oxidatively fluorinated using metal
fluorides such as CoF3, KCoF4, AgF2, CeF4, and MnF3.18–21
Unfortunately such reagents have not been found to be useful
for introducing only one or two fluorines into benzene or other
aromatics, generally acting to exhaustively fluorinate com-
pounds, with the result that saturated polyfluoro or perfluoro
compounds are usually obtained. Moreover, they require
expensive elemental F2 to prepare or regenerate. Therefore, the
discovery of a transition metal fluoride reagent that is powerful
enough to fluorinate but not so reactive as to destroy an aromatic
system and that can be regenerated without the need for F2 is
a noteworthy event.
In general, the relative fluorinating activities of transition
metal fluorides are directly related to their respective redox
potentials. For example, the fluorides of metal ions that have
E° > 1 comprise the potent group of fluorinating agents
mentioned above that give rise to exhaustive fluorination. In
contrast, fluorides of the metal ions with E° < 0, such as ZnF2,
MgF2, and AlF3, are inert towards aromatic hydrocarbons. On
the other hand, fluorides of metal ions with 1 > E° > 0, such
as CuF2, AgF, HgF2, and Hg2F2, can act as mild fluorinating
agents. In principle, all of these fluorides can be reoxidized and
the fluorides regenerated by sequential or simultaneous treatment
with O2 and HF. Among these reagents, copper(II) fluoride
appeared to have the greatest potential with respect to fluorinat-
ing benzene, as was demonstrated recently by Subramanian and
A newly synthesized copper aluminum fluoride of nominal
composition CuAl2F8 exhibits excellent reactivity towards direct
oxidative fluorination of aromatic compounds, as well as fluoro-
dechlorination of chloroaromatics. The spent CuAl2F8 reagent can
be regenerated by treatment with O2 and HF, and the fluorination
process has been demonstrated to retain high conversions through
20 reaction cycles. The main advantages of this new process are
safety, minimal waste, and potentially low cost.
Introduction
Fluorinated aromatic compounds are valuable synthetic
intermediates for the preparation of pharmaceutical drugs, agro-
chemicals, and polymers.1 However, for all practical purposes,
the only way that fluorine is currently incorporated into a
benzene ring commercially is the Balz-Schiemann reaction and
related processes involving diazonium ion chemistry2,3 or under
special circumstances by halex exchange of aromatic chlorine
by fluorine.4 The diazonium processes exhibit poor atom
economy and generate considerable waste. In the current study,
we have sought to identify and explore new, low-cost, and
environmentally benign processes for replacing aromatic hy-
drogen with fluorine.
There are already a number of fluorinating agents known
that will either electrophilically or oxidatively replace aromatic
hydrogen with fluorine,5–8 although few of them are effective
in converting relatively unreactive benzene to fluorobenzene.
These include reagents such as XeF2,6,9,10 CF3OF,7,11 CH3CO2F,7,12
* To whom correspondence should be addressed. E-mail: wrd@chem.ufl.edu.
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10.1021/op700266y CCC: $40.75
Published on Web 02/21/2008
2008 American Chemical Society
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