Tandem Fries Reaction-Conjugate Addition under Microwave Irradiation in Dry Media; One-pot Synthesis of Flavanones

Article abstract of DOI:10.1039/a902507c

An AlCl3-ZnCl2 mixture supported on silica gel is found to be an efficient medium for the Fries rearrangement of acyloxybenzene or naphthalene derivatives in solvent-free conditions under microwave irradiation.

Full text of DOI:10.1039/a902507c

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574 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 574^575y
Tandem Fries Reaction^Conjugate Addition
under Microwave Irradiation in Dry Media;
One-pot Synthesis of Flavanones
Firouz Matloubi Moghaddam,* Mohammad Ghaffarzadeh
and Seyed Hossein Abdi-Oskoui
aSharif University Technology, Department of Chemistry, P.O. Box 11365-9516, Tehran, Iran
bDepartment of Chemistry, Faculty of Science, Al-Zahra University, Vanak, Tehran, Iran
An AlCl3^ZnCl2 mixture supported on silica gel is found to be an efficient medium for the Fries rearrangement of
acyloxybenzene or naphthalene derivatives in solvent-free conditions under microwave irradiation.
Acylphenols are useful organic compounds and versatile
intermediates in the synthesis of biologically active
naphthoquinones, pesticides, photographic agents and UV
hydroxy group to the a; b-unsaturated system to a¡ord
£avanones in excellent yields. One-pot synthesis of
£avanones are of interest as £avanones are biologically
active compounds and recently, dioclein, a £avanone of
plant origin was found to be biologically active for the
treatment of kidney stones and prostate gland disorders.17
To the best of our knowledge, this is the ¢rst example
of a tandem Fries reaction^conjugate addition in dry media
under microwave irradiation. To demonstrate the e¤ciency
of this methodology, a-naphthyl acetate (Table 1 entry 6)
mixed with support, was heated to ca. 300 8C (the reaction
mixture reached this temperature in a microwave oven after
7 min.) for 7 min in an oil-bath, to give a 10% isolated
yield of the reaction product along with starting material.
3
absorbents.1
Although the Fries rearrangement of acyloxy benzenes
provides useful routes to acylphenols, a long re£ux time
with more than a stoichiometric amount of a Lewis acid
such as AlCl3 is required.4;5 Thermally conducted Fries
reactions give rise to mixtures of ortho- and para-
substituted products, the proportion of each being strongly
in£uenced by the temperature (high temperature favors
ortho-shifts) and reaction media. To overcome these
7
problems, new catalysts such as Hf(OTf)4,6 Sc(OTf)3
8
and ZrCl4 have been developed recently for this reaction.
However, with these catalysts a long re£ux time is
required and the catalysts are not readily available.
Therefore, the development of a new catalyst, which pro-
motes the Fries rearrangement cleanly and regioselectively,
is required. The e¤ciency of microwave irradiation for pro-
moting organic reactions has been demonstrated.9 In con-
Table 1 Fries rearrangement of aryl ethers
Entry
Substrate
Producta
Yieldb(%)
OH
O
tinuation of the study of microwave assisted organic
O
Me
13
Me
reactions in our research group,10
we were interested
1
2
95
97
O
in developing a new catalyst for the Fries reaction, under
microwave irradiation. Also the use of microwave
irradiation for this reaction is known to be e¡ective but
was not ideal, requiring in our hands, more than one equiv-
alent of AlCl3 in chlorobenzene and use of a sealed tube,
and was not regioselective for non-substituted phenyl
acetate.14 Also the high pressure developed in the sealed
tube may cause hazards. It appeared the Lewis acids
supported on a solid phase might be good alternative con-
dition for this reaction in dry media.15 We have found that
an AlCl3^ZnCl2 mixture supported on silica gel is an
e¤cient medium for promotion of the Fries rearrangement
without solvent under microwave dielectric heating. It
should be noted that, the reaction does not proceed on
ZnCl2 or AlCl3 supported on silica gel alone.
O
Me
OH
O
O
Me
Me
Me
Me
OH
O
O
Ph
3
4
90
62
O
O
O
Me
Ph
Me
OH
O
MeO
O
MeO
Me
OH
O
Me
90
5
O
O
Me
O
HO
Me
O
When neat phenyl acetate was mixed with the support
(1 : 3, w/w)16 and subjected to microwave irradiation for
7 min, after work-up a 95% yield of the ortho-directed prod-
uct (20-hydroxyacetophenone) was obtained. Several further
examples have been investigated. In most cases a single
product derived from the ortho-shift of the acyl group to
the sterically less encumbered neighboring carbon center
was obtained (Table 1).
O
O
Me
OH
Me
95
80
6
Ph
O
O
O
Me
Ph
OH
7
Interestingly, when a cinnamyl ester of phenols and
O
O
naphthols (Table 2) was used as
a substrate, the
Me
O
ortho-rearranged product chalcone spontaneously cyclized
by intramolecular conjugate addition of the phenolic
OH
8
92
* To receive any correspondence.
aAll products were characterized by mp, IR, 1H NMR, and their
spectroscopic data were similar to those reported in the literature.
bAll yields refer to isolated products.
This is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).

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J. CHEM. RESEARCH (S), 1999 575
Table 2 Fries rearrangement of cinnamyl esters
in vacuo and the gel left to stand at 120 8C overnight. The resulting
solid granules were ground and further activated by heating to 230 8C
in vacuo. The catalyst was stored under dry conditions.
Time/min.
(% Yield)a
Entry
Substrate
Product
1
Compound 1: mp 104 8C (from ethanol): IR (KBr) nmax=cm 3030,
2923, 2861, 1700 (CˆO), 1615, 1492, 1299, 1230, 838, 700: dH
(80 MHz, CDCl3) 2.46 (s, 3H, CH3), 2.9 (ABX system, 2H,
JAX ˆ 4:72, JBX ˆ 11:38, JAB ˆ 25:85 Hz), 5.4 (dd, 1H, J ˆ 4:77,
O
O
Ph
O
‡
11.4 Hz), 7.04±7.90 (m, 8H, aromatic); MS (70 eV) m/z 238 (M ,
1
7 (87)
100), 161 (19.5), 134 (6.4), 104 (22%).
Me
1
Compound 2: mp 136 8C (from ethanol): IR (KBr) nmax=cm 3007,
O
2961, 2930, 2830, 1676 (CˆO), 1484, 1353, 1284, 1168, 1038, 869,
776, 715; dH (80 MHz, CDCl3) 2.87 (ABX system, 2H, JAX ˆ 4:87,
JBX ˆ 11:38, JAB ˆ 25:67 Hz), 3.74 (s, 3H, OCH3), 5.35 (dd, 1H,
J ˆ 4:87, 11.37 Hz), 6.9±7.50 (m, 8H, aromatic); MS (70 eV) m/z 254
Me
1
O
O
Ph
O
‡
(M , 81.6), 177 (19.3), 150 (100), 135 (8.4), 122 (9.5), 107 (16.5), 103
7 (73)
2
(12.85).
1
MeO
Compound 3: mp 126 8C (from ethanol): IR (KBr) nmax=cm 3053,
O
2961, 2923, 1676 (CˆO), 1589, 1438, 1338, 1192, 1115, 823, 700; dH
(80 MHz, CDCl3) 3.1 (ABX system, 2H, JAX ˆ 4:95, JBX ˆ 11:51,
JAB ˆ 25:83 Hz), 5.63 (dd, 1H, J ˆ 4:96, 11.57 Hz), 7.30±8.5 (m,
OMe
O
2
‡
11H, aromatic); MS (70 eV) m/z 274 (M , 66), 197 (9), 170 (100), 142
(6.7), 114 (43.3), 103 (9.5), 77 (4).
O
Ph
1
Compound 4: mp 114 8C (from ethanol): IR (KBr) nmax=cm 3061,
O
3
4
7 (85)
3030, 2969, 1653 (CˆO), 1600, 1515, 1483, 1376, 1238, 1007, 830,
753, 700; dH (80 MHz, CDCl3) 2.95 (ABX system, 2H, JAX ˆ 4:5,
JBX ˆ 12:44, JAB ˆ 28:96 Hz), 5.47 (dd, 1H, J ˆ 4:49, 12.28 Hz),
7±7.90 (m, 10H, aromatic) 9.41 (d, 1H peri-hydrogen); MS (70 eV)
O
3
‡
m/z 274 (M , 72.6), 246 (6), 198 (14.8), 170 (100), 142 (41), 114 (72),
104 (19.5), 88 (11), 77 (12).
O
Ph
O
7 (79)
O
Received, 29th March 1999; Accepted, 10th June 1999
Paper E/9/02507C
O
4
aYields refer to isolated products.
References
1
2
3
D. J. Crouse, S. L. Hurlbut and M. S. Wheeler, J. Org. Chem.,
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For recent reviews, see: S. Caddick, Tetrahedron, 1995, 51,
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Comparison with a 95% yield for the same period under
microwave condition shows that the reaction is at least ten
times faster. Furthermore, when the reaction mixture was
heated at 300 8C for a longer period (60 min), a tarry
material was obtained owing to decomposition of both
product and starting material. In conclusion, we have
4
5
6
7
8
9
developed
a new support, which promotes the Fries
rearrangement of aryl esters under microwave irradiation
in dry media. The reaction proceeded smoothly with
excellent yield and regioselective acylation of phenols
and naphthols were achieved. The ease of work-up is
another advantage of this new methodology.
10 F. Matloubi Moghaddam, A. Shari¢ and M. R. Said, J. Chem.
Res. (S), 1996, 338.
11 F. Matloubi Moghaddam and A. Shari¢, Synth Commun.,
1995, 25, 2457.
12 F. Matloubi Moghaddam and M. Gha¡arzadeh, Tetrahedron
Lett., 1996, 37, 1855.
13 F. Matloubi Moghaddam and R. Emami, Synth. Commun.,
1997, 27, 4073.
14 V. Sridari and V. S. Sundara Rao, Indian J. Chem. Sect. B,
1994, 33, 184.
15 J. H. Clark, in Catalysis of Organic Reactions by Supported
Inorganic Reagents, VCH, New York, 1994 and references
cited therein.
16 The minimum amount of supported reagent to substrate was
found to be 3 : 1 (w/w) after performing several experiments
and optimization.
Experimental
General.öThe starting materials were prepared by treatment of
acid chlorides with phenols or naphthols in the presence of sodium
hydroxide.18 1H NMR spectra were recorded on a Bruker FT-80
AC spectrometer. Mass spectra were obtained on a Fisson 800 Trio
GC-MS with an ionizing voltage of 70 eV. IR spectra were performed
on a Mattson 1000 spectrometer. Melting points were determined on a
Mettler FPS and are uncorrected.
General Procedure for Microwave-induced Fries Rearrange-
ment.öNeat substrate (0.01 mol) was mixed with the support (1 : 3,
w/w) in a beaker and was exposed to microwave irradiation for 7 min.
After cooling to room temperature the product was extracted with
diethyl ether. Evaporation of the solvent gave almost pure product.
Further puri¢cation was carried out by recrystallisation or column
chromatography on silica gel.
17 P. Spearring, G. Majetich and J. Bhattacharyya, J. Nat. Prod.,
1997, 60, 399.
Preparation of the Support.öTo 100 g of SiO2: AlCl3 Á 6H2O:
ZnCl2 (5:4:1 w/w/w), was added 150 ml of water and the product
well mixed19 to give a gel-like material. The water was evaporated
18 Vogel's Textbook of Practical Organic Chemistry, 4th edn.,
1978, p. 751.
19 Silica gel (Merck, Art. No. 7734, mesh 70^230).