Acylation of activated aromatics without added acid catalyst
James S. Brown, Roger Gläser, Charles L. Liotta and Charles A. Eckert*
Schools of Chemical Engineering, Chemistry and Biochemistry, and Specialty Separations Center, Georgia Institute
of Technology, Atlanta, GA 30332-0100, USA. E-mail: cae@che.gatech.edu
Received (in Covallis, OR, USA) 24th February 2000, Accepted 15th May 2000
Published on the Web 26th June 2000
Phenol and resorcinol can be acetylated to the corresponding
esters and ketones in aqueous and neat acetic acid at high
temperature (250–300 °C) to substantial equilibrium conver-
sion without any added acid catalyst.
We have successfully acetylated phenol and resorcinol in
nearcritical water, as well as in neat acetic acid, in the
temperature range 250–300 °C without any added acid catalyst
or UV light. Performing Friedel–Crafts acylations and Fries-
rearrangements in neat or aqueous acetic acid at elevated
temperatures is also attractive as no additional organic solvent is
required, and any unused acetic acid may be recycled for further
reaction.
The reactions were performed in 3.2 ± 0.2 ml titanium batch
vessels as described elsewhere.16 Each vessel was loaded with
phenol or resorcinol, an excess of acetic acid (Aldrich, HPLC
grade), and, in certain experiments, deoxygenated water
(Aldrich, HPLC grade). For reactions in neat acetic acid, the
molar ratio of reactant to acetic acid was 1:50. For reactions in
aqueous acetic acid, the molar ratio of reactant to acetic acid to
water was 1 12 47, respectively. Products were identified by
GC–MS (EI mode) and by comparison of the GC retention
times and EI mass spectra to those of commercially available
compounds. The composition of the each product mixture was
quantified by GC-FID.
The Friedel–Crafts alkylations of phenol and p-cresol with
tert-butyl alcohol in nearcritical water previously reported16,17
were found to be reversible, with equilibrium yields of ca. 20
mol%. In this work, we report that the acetylations of phenol
and resorcinol are also reversible at high temperature in the
presence of water, but with less favorable equilibrium yields.
These acylations are generally irreversible with traditional
Friedel–Crafts catalysts due to the complexation of the acid
catalyst with the carbonyl oxygen of the product. In this work,
however, products were not stabilized by complexation with
catalyst and were free to react back to starting material. In
aqueous acetic acid at 290 °C, phenol was primarily converted
to 2A-hydroxyacetophenone, 4A-hydroxyacetophenone, and
phenyl acetate in roughly equal amounts, with a combined
equilibrium yield of less than 1%. Under the same conditions,
resorcinol was converted to primarily 2,4-dihydroxy-
acetophenone (Scheme 1) with a modest equilibrium yield of
4%.
Friedel–Crafts and other acylations generally require stoichio-
metric quantities of strong mineral acids, such as H2SO4,
H3PO4, and HCl, or nonregenerable Lewis acids, such as
AlCl3.1 These acids require neutralization and disposal, and
disposal costs can be considerable. The conventional acylation
of one mol of phenol with acetic acid consumes stoichiometric
quantities of AlCl3. Neutralizing this AlCl3 requires land-filling
several pounds of Al(OH)3 salt for every pound of product
produced.2,3 In addition, many of these reactions require polar
organic solvents, such as methylene chloride, that can simulta-
neously dissolve the reactants as well as the reactant–catalyst
complex.1,3
Aromatic acylations have also been performed successfully
without salt production over solid acids, such as zeolites,4 as
well as polymer supported alkyl sulfonic acid.5 Heterogeneous
catalysis of this type, however, generally requires the operating
expense of vaporizing the reactant and the increased capital cost
of the large vessels needed for solid–vapor contacting. In
addition, the need for periodic regeneration or replacement of
the rapidly deactivating zeolite catalysts may preclude their use
in commercial applications where reactants readily form coke.
Ghibaudi and Colassi attempted the Fries rearrangement of
phenyl acetate at low pressure and very high temperatures (T >
675 °C) without catalyst, but only phenol and ketene were
detected as products.6 Photo-Fries rearrangements of phenyl
acetate7 and 2,5-dimethylphenyl acetate8 have been run suc-
cessfully to produce the corresponding ketones.
Another alternative to acid catalysts that require neutral-
ization and disposal are polar-protic solvents at elevated
temperature that can simultaneously act as the solvent, catalyst,
and, in certain cases, the reactant. Liquid water (Tc = 374 °C)
in the nearcritical region (250–300 °C) exhibits some beneficial
properties that make it a good solvent and catalyst for acid-
catalyzed organic reactions. As the temperature is increased
from room temperature to 275 °C, the dieletric constant
decreases from 80 to 20, and nearcritical water readily dissolves
both organic and ionic compounds. Even non-polar organics,
such as toluene, become miscible above 300 °C.9–10 In addition,
the dissociation constant of water increases by three orders of
magnitude from room temperature to 275 °C, making it a source
of hydronium and hydroxide ions that may catalyze reactions.
Nearcritical water has been used as a solvent, catalyst, and
reactant for a number of hydrolyses that require added mineral
acid at ambient conditions.9,12–15 It has also been successfully
used for the Friedel–Crafts alkylation of phenol and p-cresol
with tert-butyl alcohol.16
To determine the effect of water on the equilibrium limitation
of these reactions, the stability of the products was checked in
water at nearcritical conditions. The product of the forward
reaction of resorcinol and acetic acid, 2,4-dihydroxyacetophe-
none, was placed in liquid water at 250 °C. The concentration
Nearcritical acetic acid (Tc = 319 °C) is another polar, protic
solvent that may simulatenously act as the solvent, catalyst, and
reactant in some reactions. Similar to nearcritical water,
nearcritical acetic acid readily dissolves organics, and it has a
higher acid strength and dissociation constant than water.
Acetic acid can also be distilled from reaction products unlike
other Lewis acid catalysts, such as AlCl3, that require
neutralization to salts and subsequent disposal.
Scheme 1
DOI: 10.1039/b001544j
Chem. Commun., 2000, 1295–1296
This journal is © The Royal Society of Chemistry 2000
1295
Brown, James S.
