Regioselective ortho-acylation of phenol and naphthol derivatives catalyzed by FeCl3 under microwave conditions

Article abstract of DOI:10.1134/S1070428007120032

Phenol and naphthol derivatives were subjected to regioselective solvent-free ortho-acylation with organic acids in the presence of FeCl ₃ under microwave irradiation. The reactions were complete in a short time, and the products were obtained in high yields.

Full text of DOI:10.1134/S1070428007120032

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 12, pp. 1757–1759. © Pleiades Publishing, Ltd., 2007.
Published in Russian in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 12, pp. 1756–1758.
Regioselective ortho-Acylation of Phenol and Naphthol
Derivatives Catalyzed by FeCl under Microwave Conditions*
3
H. Naeimi and L. Moradi
Chemistry Department, Faculty of Sciences, Kashan University, Kashan, 87317, I.R. Iran
fax: +98361552935; e-mail: naeimi@kashanu.ac.ir
Received November 1, 2005
Abstract—Phenol and naphthol derivatives were subjected to regioselective solvent-free ortho-acylation with
organic acids in the presence of FeCl under microwave irradiation. The reactions were complete in a short
3
time, and the products were obtained in high yields.
DOI: 10.1134/S1070428007120032
Development of regioselective reactions of aromat-
ic compounds is a fundamental but still important
theme in organic synthesis. For example, ortho-acyla-
tion of phenol and naphthol derivatives provides useful
synthetic methods for the preparation of 2-hydroxy-
phenyl or 2-hydroxynaphthyl ketone derivatives [1],
which are key intermediates in the synthesis of bio-
logically active naphthoquinone derivatives [2], naph-
thalene-containing liquid crystalline polymers, and low
molecular weight mesogens [3]. Hydroxyaryl ketones
are widely used in perfumery, metallurgy, and pharma-
ceutics. Moreover, compounds of this class are also
important synthetic intermediates [4].
We previously reported [14] on the acylation of
phenols and naphthols into the ortho position with
carboxylic acids in the presence of some Lewis acids
under microwave irradiation. The present communica-
tion describes the results of using microwave irradia-
tion in the acylation of phenol and naphthol derivatives
in the presence of FeCl . Initially we examined acyla-
3
tion of hydroxyaryl compounds with acetic acid in
the presence of FeCl under microwave irradiation
3
(
Scheme 1). The reactions were carried out without
a solvent, and the corresponding ortho-acylated phenols
and naphthols were obtained with high yields in a very
short time (1–3 min; Table 1). The data in Table 1
Although some hydroxyaryl ketones exist in the
nature, unnatural hydroxyaryl ketones have been
synthesized by several methods from phenols and
naphthols. Among these, Friedel–Crafts acylation of
phenol and naphthol derivatives in the presence of
Lewis acids is one of the common routes to these
compounds [5]. The acylation can also be achieved by
treating the free acid with a variety of condensing
agents such as hydrogen fluoride [6], concentrated sul-
furic acid [7], phosphorus(V) oxide [8], polyphos-
phoric acid [9], fluorosulfonic acid [10], and methane-
sulfonic acid on alumina [11].
show that the use of FeCl ensures very high yields and
3
regioselectivity: in most cases no para-acylated prod-
ucts were formed. For example, 2,6-dimethylphenol
failed to produce the corresponding para-acyl deriva-
tive under the given conditions (run no. 10). It should
also be noted that ortho-acylated products were not
obtained from substrates having electron-withdrawing
substituents, such as m- and p-nitrophenols and 1,4-di-
hydroxy-9,10-anthraquinone (run nos. 4, 7, 12). The
yields of 2-acetyl-1-hydroxynaphthalene and 1-acetyl-
2
-hydroxy naphthalene from the corresponding naph-
Aromatic acylation with carboxylic acids instead of
acid anhydrides and acyl chlorides has attracted atten-
tion because it is an environmentally benign reaction
leading to formation of water as the only by-product
Scheme 1.
OH
OH
O
FeCl , MW
3
Me
+
CH CO H
3 2
[
12]. On the other hand, microwave-assisted solvent-
free organic syntheses [13] have aroused growing in-
terest as efficient, economic, and clean procedures.
R
R
R = 2,3-benzo, 3,4-benzo, m-Me, p-Me, m-OH, p-OH,
m-O N, p-O N, o,p-Me (see Table 1).
*
The text was submitted by the authors in English.
2
2
2
1757

1
758
NAEIMI, MORADI
Table 1. Acylation naphthol and phenol derivatives with 1.2 mmol of acetic acid in the presence of FeCl
3
under microwave
irradiation
a
Run no.
Substrate
Substrate, mmol
FeCl
3
, mmol
Power, W
Time, min
Yield, %
0
0
0
0
0
0
0
0
0
1
1
1
2
3
4
5
6
7
8
9
0
1
Naphthalen-1-ol
Naphthalen-2-ol
p-Cresol
0.69
0.69
0.95
0.76
0.95
1.06
0.76
0.90
0.90
0.82
0.83
0.31
0.31
0.31
0.62
0.31
0.31
0.31
0.31
0.31
0.62
0.31
500
600
400
700
400
600
700
300
300
700
300
>2>
60
35
95
00
98
70
00
98
98
00
60
>2>
2
m-Nitrophenol
m-Cresol
3
2
Phenol
3
p-Nitrophenol
Resorcinol
2
00.1.33
1
Hydroquinone
2,6-Dimethylphenol
2,4-Dimethylphenol
3
>1>
1
2
1,4-Dihydroxy-9,10-
anthraquinone
0.84
0.62
800
3
00
a
Yield of the pure product isolated by chromatography on silica gel.
thols (run nos. 1, 2) were lower as compared to phenol
derivatives due to lower reactivity of the former.
thermal conditions at the same temperature as under
microwaves. However, no acylated products were
formed after a long time.
We also examined acylation of p-cresol with other
organic acids, such as propanoic, butanoic, and pen-
tanoic (Scheme 2). The results are given in Table 2; it
is seen that the yields of the corresponding ortho-acyl
derivatives are very high.
The structure of the products as ortho-acyl deriva-
tives is confirmed by the presence in their IR spectra of
a broadened absorption band from O–H stretching vi-
–
1
brations in the region 3100–3500 cm and of a strong
–
1
carbonyl absorption band at 1620–1670 cm . Their
Scheme 2.
1
H NMR spectra contained a broadened singlet at
OH
OH
O
δ 11.8–13.8 ppm from the hydroxy proton.
FeCl , MW
R
We can conclude that the described procedure for
ortho-acylation of phenols and naphthols is advanta-
geous due to its simplicity, high regioselectivity and
yield, short reaction time, and easy work-up.
3
+
RCO H
2
Me
Me
3 2 5 3 7 4 9
R = CH , C H , C H , C H .
EXPERIMENTAL
To check for possible intervention of any non-
purely thermal specific microwave effect, we tried to
perform analogous reactions under conventional
General procedure for ortho-acylation of phenol
and naphthol derivatives in the presence of FeCl3
under microwave irradiation. A mixture of the cor-
responding phenol or naphthol, iron(III) chloride, and
organic acid (for amounts of the reactants, see Tables 1
and 2) was irradiated in a microwave oven for a time
indicated in Table 1 or 2. The progress of the reaction
was monitored by TLC. After cooling to room tem-
perature, the mixture was dissolved in 10 ml of meth-
ylene chloride, and the solution was washed with water
Table 2. Acylation of 0.95 mmol of p-cresol with various
organic acids in the presence of FeCl
3
under microwave
irradiation
FeCl
3
,
Time, Power, Yield,
Acid (mmol)
CH CO H (1.2)
mmol
0.31
0.31
0.32
0.32
min
W
%
98
98
90
85
3
2
2
400
600
600
600
2
C H
3
C H
4
C H
5
7
9
CO
2
2
2
H (1.3)
1
(
~20 ml) and aqueous NaHCO (20 ml) to remove
3
CO
CO
H (1.08)
H (0.95)
1
excess organic acid, filtered, and evaporated. The resi-
due was purified by chromatography on silica gel
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 12 2007

REGIOSELECTIVE ortho-ACYLATION OF PHENOL AND NAPHTHOL DERIVATIVES
1759
using petroleum ether as eluent. The products were
identified by comparing their spectral parameters and
physical constants with those reported in [4, 15–17].
7. Haword, R.D., J. Chem. Soc., 1932, p. 1125.
8. Cook, J.W., J. Chem. Soc., 1932, p. 1472.
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1
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0. Baker, W., Coates, G.E., and Glockling, F., J. Chem.
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1. Sharghi, H. and Kaboudin, B., J. Chem. Res., Synop.,
The authors thank the Research Council of Kashan
University for partial support of this work.
1
998, p. 628.
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