PAPER
1789
Selective Fries Rearrangement Catalyzed by Zinc Powder
Selective Fries
a
Rearrange
t
ment
C
y
atalyzedby
ainc Powder Paul,* Monika Gupta
Department of Chemistry, University of Jammu, Jammu-180 006, India
Fax +91(191)2505086; E-mail: paul7@rediffmail.com
Received 9 January 2004; revised 26 April 2004
In our earlier communication,21 we have shown that zinc
catalyzes acylation of aromatic substrates efficiently in
solvent-free conditions under microwave irradiation.
These findings encouraged us to study the Fries rearrange-
Abstract: Zinc powder in the presence of N,N-dimethylformamide
efficiently catalyzes the selective Fries rearrangement of acetylated
phenols under microwave heating or with conventional heating us-
ing an oil bath. In some cases different products were obtained using
microwave heating and conventional heating. Selective migration ment of acetylated phenols, a reaction similar to above re-
of the acyl group has been noted with good yields.
action using zinc powder in the presence of DMF under
both microwave irradiation and oil-bath heating. A variety
of acetylated phenols have been shown to undergo Fries
rearrangement selectively at one position and we were
able to isolate single isomer in quite a good yield. In some
cases, different isomers (entries 1, 2, 4, 5, 9, 10) were
formed using microwave and oil-bath heating. Although
oil-bath heating takes longer time with comparable yields,
yet the importance of zinc catalyst is reflected in the way
that single isomer was obtained under both microwave
and oil-bath heating.
Keywords: acetylated phenols, zinc powder, Fries rearrangement,
microwave activation, selectivity
Among
Friedel–Crafts
reactions,1
the
Fries
rearrangement2 is an important process for the conversion
of acetylated phenols to hydroxy acetophenones. It is used
in the manufacture of important pharmaceuticals includ-
ing acetaminophen and salbutamol,3 UV adsorbents4 and
pesticides.5
Fifteen acetylated phenols (entries 1–15) were tested for
Fries rearrangement using Zn powder as catalyst and
DMF as energy transfer medium/solvent both under mi-
crowave irradiation as well as oil-bath heating (see the ex-
perimental section). The results are shown in Table 1. In
case of phenyl acetate (entry 1), o-hydroxyacetophenone
was obtained in 75% isolated yield when irradiated in a
microwave oven for three minutes. However, when the re-
action was carried out with same quantities in an oil-bath
at 60 °C (temperature noted at the end of exposure during
the microwave experiment) for six hours, p-hydroxyace-
tophenone was obtained in 70% isolated yield, whereas, a
mixture of o- and p-hydroxyacetophenone was reported13
earlier under microwave irradiation. When the Fries rear-
rangement of phenyl acetate was attempted using Zn pow-
der by stirring at 110 °C in toluene using oil-bath, no
reaction was observed on TLC up to six hours. When (2-
Methylphenyl) acetate (entry 2) was subjected to the mi-
crowave irradiation for five minutes using Zn powder and
DMF, exclusive p-migration took place and 4-hydroxy-3-
methylacetophenone was obtained in 74% isolated yield.
However, when the same reaction was carried out in an
oil-bath at 68 °C (temperature noted at the end of exposure
during microwave experiment) for 45 minutes, exclusive
o-migration took place with 70% isolated yield of 2-hy-
droxy-3-methylacetophenone. Earlier it was reported14
that when (3-methylphenyl) acetate was subjected to Fries
rearrangement using K-10 montmorillonite under micro-
wave irradiation, a mixture of ortho/para isomers was ob-
tained in the ratio of 7:3. With anhydrous AlCl3 at 165 °C,
o-migration takes place exclusively.14 However, when (3-
methylphenyl) acetate (entry 3) was irradiated in a micro-
wave oven in the presence of zinc powder and N,N-di-
The Fries rearrangement is generally catalyzed by highly
corrosive, hazardous and polluting Lewis acids, such as
AlX3 (X = Cl, Br or I), BF3, TiCl4, FeCl3, ZnCl2, ZrCl4,
SnCl4, commonly employed in amounts of more than one
equivalent. As water quenching is necessary at the end of
the reaction, the process leads to large volumes of hazard-
ous waste.1,3 Some alternative solid acid catalysts includ-
ing zeolites,6,7 transition metal triflates,8 sulfated
zirconia,9 ionic melts,10 and solid sulfonated resins7,11
have been reported for these reactions. These catalysts
generally suffer from low activity, low selectivity and poi-
soning of the catalyst and its subsequent deactivation. Re-
cently, some Fries rearrangements have been reported
under microwave irradiation using AlCl3–ZnCl2 support-
ed on silica gel,12 aluminum chloride13 and K10 montmo-
rillonite.14 Thus, there remains a need to find a new
environmentally benign procedure, which should be sim-
ple, safe and economic, for the Fries rearrangement.
The coupling of microwave irradiation15 with the use of
catalysts or mineral-supported reagents provides chemical
processes with special attributes such as enhanced reac-
tion rates, higher yields, greater selectivity and improved
ease of manipulation.
Zinc powder is non-toxic and inexpensive. It has been
used for selective a-haloacylation and gem-bisacylation
of alkyl aldehydes,16 synthesis of o-arylenedizinc com-
pounds,17 synthesis of benzhydrols,18 transesterification
of b-ketoesters,19 acylation and sulfonation of pyrrole.20
SYNTHESIS 2004, No. 11, pp 1789–1792
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Advanced online publication: 13.07.2004
DOI: 10.1055/s-2004-829152; Art ID: Z00404SS
© Georg Thieme Verlag Stuttgart · New York