Solvent-free synthesis of 2-amino-3-aryl-5-substituted thiophenes as anti-inflammatory agents using KF-Al2O3 under microwave irradiation

Article abstract of DOI:10.1080/00397910801997843

The synthesis of 2-amino-3-aryl-5-substituted thiophenes as anti-inflammatory agents catalyzed by KF-Al2O3 under microwave irradiation is reported. Copyright Taylor & Francis Group, LLC.

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Solvent-Free Synthesis
of 2-Amino-3-aryl-5-
substituted Thiophenes as Anti-
inflammatory Agents using
KF-Al2O3 under Microwave
Irradiation
Hamdollah Saeidian a , Azam Sadeghi a , Zohreh
Mirjafary a & Firouz Matloubi Moghaddam a
a Sharif University of Technology, Department of
Chemistry, Laboratory of Organic Synthesis and
Natural Products , Tehran, Iran
Published online: 13 Jun 2008.
To cite this article: Hamdollah Saeidian , Azam Sadeghi , Zohreh Mirjafary & Firouz
Matloubi Moghaddam (2008) Solvent-Free Synthesis of 2-Amino-3-aryl-5-substituted
Thiophenes as Anti-inflammatory Agents using KF-Al2O3 under Microwave Irradiation,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 38:12, 2043-2053, DOI: 10.1080/00397910801997843
To link to this article: http://dx.doi.org/10.1080/00397910801997843
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Synthetic Communications1, 38: 2043–2053, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910801997843
Solvent-Free Synthesis of 2-Amino-3-aryl-5-
substituted Thiophenes as Anti-inflammatory
Agents using KF-Al2O3 under Microwave
Irradiation
Hamdollah Saeidian, Azam Sadeghi, Zohreh Mirjafary,
and Firouz Matloubi Moghaddam
Sharif University of Technology, Department of Chemistry, Laboratory
of Organic Synthesis and Natural Products, Tehran, Iran
Abstract: The synthesis of 2-amino-3-aryl-5-substituted thiophenes as anti-
inflammatory agents catalyzed by KF-Al2O3 under microwave irradiation is
reported.
Keywords: 2-Amino-3-aryl-5-substituted thiophenes; Anti-inflammatory agents;
KF-Al2O3; Microwave irradiation
INTRODUCTION
The effort to develop novel drug-designing strategies has attracted
great interest in the pharmaceutical industry and organic synthesis.
Microwave-assisted solid-phase organic synthesis (MW-SPOS) has been
regarded as one of the new important fields in synthetic organic chemis-
try. MW-SPOS techniques offer a powerful strategy for the discovery and
generation of lead heterocyclic compounds. In addition, a solid-phase
approach is interesting because the reaction can be driven to completion
by using excess reagents, which are subsequently removed by simple fil-
tration. On the other hand, the advantages of the microwave irradiation
includes not only improving classical reactions but also shortening
Received in the U.K. September 18, 2007.
Address correspondence to Firouz Matloubi Moghaddam, Shariff University
of Technology, Department of Chemistry, P. O. Box 11155-9516, Tehran. E-mail:
matloubi@sharif.edu
2043

2044
H. Saeidian et al.
reaction times, improving the yields, and suppressing by-product forma-
tion as compared with conventional thermal heating.[1–6] There are many
reports in the literatures about the synthesis of heterocyclic compounds by
solid supports under microwave heating,[7] whereas the synthesis of thio-
phenes derivatives has received less attention under these conditions. Our
interest in this class of compound was based on its use as novel nonster-
oidal anti-inflammatory drugs (NSAIDs) having general formula (A).[8,9]
Several methods have been described for the synthesis of this
framework. The reaction of organometallic derivatives of 2-H-substituted
thiophenes with suitable carboxylating reagents afforded thiophene-2-
carboxylic acids, which can be transformed into corresponding ketones
by standard methods.[10] Another method for introducing acyl group on
thiophene derivatives is the Vilsmeier–Haack reaction.[11] An N,N-dialky-
lamide reacts with phosphorus oxychloride or oxalyl chloride to give a
chloroiminium ion, which is the reactive electrophile. This species acts
as an electrophile in the absence of any added Lewis acid, but only rings
with electron-releasing substituents are reactive (Scheme 1).
Friedel–Crafts (FC) acylation has also been used for the prepara-
tion of acylthiophenes. The FC acylation of thiophenes fails if amino-
substituted thiophenes are used as starting materials.[12] Therefore,
2-amino-3-aryl-5-substituted thiophenes (A) cannot be prepared by FC
acylation. The most convenient method for preparing thiophene with a
high degree of functionality is the Gewald method, in which elemental
sulfur is reacted with an activated acetonitrile and an aldehyde, ketone,
or 1,3-dicarbonyl compound in the presence of a base.[13] A modification
of the Gewald method has been reported in which an alkoxyacetone is
reacted with ethyl cyanoacetate, sulfur, and morpholine, producing most
sources of alkoxy thiophene derivatives in poor yields (19–39%).[14]
Scheme 1. Vilsmeier–Haack reaction.

2-Amino-3-aryl-5-Substituted Thiophenes
2045
Scheme 2. Solvent-free synthesis of 2-amino-3-aryl-5-substituted thiophenes: i,
HN(CH2-CH2)2O=Sg; ii, HN(CH2-CH2)O=HC(OCH2-CH3)3; iii, CH2Cl2; iv,
Br2=CH3COOH; and v, KF-Al2O3=microwave irradiation.
Recently some methods for preparing 2-amino-3-aryl-5-substituted
thiophenes were published.[9,15] Although the reported methods give high
yield, these methods have not been used for synthesis of 2-amino-3-aryl-
5-amido thiophenes. On the other hand, the toxic and volatile nature of
many organic solvents, which are widely used in organic synthetic
procedures, has posed a serious threat to the environment.
In continuation of our research in this area,[16–24] herein we report
a new and efficient KF-Al2O3-catalyzed solvent-free protocol for the
synthesis of 2-amino-3-aryl-5-substituted thiophenes as new anti-
inflammatory drug candidates under microwave irradiation (Scheme 2).
To the best of our knowledge, this is the first demonstration of the
synthesis of 2-amino-3-aryl-5-amido thiophenes.
First experiments focused on the optimized of the amount of
KF-Al2O3. The results are summarized in the Table 1. We found that
0.25 g of KF-Al2O3 could effectively catalyze the reaction for 1 mmol
of 3 and 1 mmol 4 to produce the desired product (Table 1, entries 7,
8). While comparing the effect of catalysts for the reaction of 3 with 4,
we found that, KF-Al2O3 was more effective than KOH-Al2O3 or
K2CO3 (Table 1, entries 3, 4).
Using more KF-Al2O3 has less effect on the yield and time of the
reaction. As shown in Table 1, the use of KF-Al2O3 offers a convenient,
environmentally friendly alternative to conventional reactions. Clearly,
the reaction time by microwave irradiation has been reduced 60 times
with higher yield than conventional heating (65% versus 50%, Table 1,
entries 8, 11). Because the product of interest is not covalently bound
to the solid support, monitoring of the reactions and analysis can be
accomplished by using standard methods [thin-layer chromatography

2046
H. Saeidian et al.
Table 1. Reaction of 3 with 4 under different conditions
Mode of
heating
Temperature Time Yield
(ꢀC)
Entry
Catalyst (g)
No catalyst
No catalyst
K2CO3 (0.25)
KOH-Al2O3 (0.25)
KF-Al2O3(1)
KF-Al2O3(0.5)
KF-Al2O3(0.25)
KF-Al2O3(0.25)
KF-Al2O3(0.25)
KF-Al2O3(0.25)
KF-Al2O3(0.25)
KF-Al2O3(0.25)
Solvent
(min) (%)
1
2
3
4
5
6
7
8
9
D
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
C6H5CH3
80
80
80
80
80
80
60
80
80
50
80
50
420 Trace
MW
MW
MW
MW
MW
MW
MW
MW
MW
D
7
7
7
Trace
50
55
7
7
70
66
7
7
63
65
7
7
55
42
10
11
12
CH2Cl2
C6H5CH3
CH2Cl2
420
420
50
40
D
1
(TLC), column chromatography, H NMR, etc.]. Finally, the products
are isolated by column chromatography, eliminating the need for a cleav-
age step, which is required in solid-phase synthesis. To generalize this
methodology, we subjected a series of substrates to the reaction to obtain
the corresponding thiophenes under the optimized reaction conditions
(Tables 2 and 3).
The variations in the yields were very little, and substituted aromatic
amides such as 4-chloro and 3-methyl gave the substituted thiophenes in
excellent yields.
The applicability of the present methodology is further extended by
performing the reaction of 3 with 5 for the synthesis of 2-amino-3-aryl-
5-acyl=carboxylate thiophenes. The reaction was performed well, and
the reaction rates as well as the yields of products were satisfactory.
A proposed mechanism for the reaction course is shown in
Scheme 3. Component 3 undergoes an S-alkylation with a-haloamide 4
or a-haloketone=ester 5, affording the iminium ions I; then subsequent
treatment with KF-Al2O3 leads to cyclization and formation of the
thiophene ring with elimination of morpholine.
To confirm the proposed mechanism, the reaction of the benzyl bro-
mide with 3 (Ar: phenyl) in the presence of H2O was studied for trapping
the iminium ion I (Scheme 4).
Indeed, the iminium ion I was hydrolyzed by the presence of water in
the reaction medium to 8, which was isolated and its structure confirmed
(see Spectral Data section).
In conclusion, the alumina-supported potassium fluoride shows high
catalytic activities for the synthesis of 2-amino-3-aryl-5-substituted

2-Amino-3-aryl-5-Substituted Thiophenes
2047
Table 2. Synthesis of 2-amino-3-aryl-5-substituted thiophenes under optimized
conditions
Entry
6a
Ar
Ar’
Produce
Mp (ꢀC) Yield (%)
Phenyl 3-Methylphenyl
171–173
65
6b
6c
Phenyl 4-Chlorophenyl
239–241
60
Phenyl 1-Naphthyl
181–183
55
thiophenes under solvent-free conditions by microwave irradiation. This
procedure offers several advantages including low loading of catalyst,
high yields, clean reaction, and use of various substrates, which make it
a useful and attractive strategy for the synthesis of 2-amino-3-aryl-5-
substituted thiophenes. These materials have the potential to be used as
novel nonsteroidal anti-inflammatory drugs.
EXPERIMENTAL
The compounds gave all satisfactory spectroscopic data. A Bruker
(DRX-500 Avance) NMR instrument was used to record the 1H
NMR and 13C NMR spectra. All NMR spectra were determined in
CDCl3 at ambient temperature. Melting points were determined on a
Buchi B540 apparatus. GC-MS (EI), 70 ev, HP6890 column: HP-5

2048
H. Saeidian et al.
Table 3. Synthesis of 2-amino-3-aryl-5-acyl/carb oxylate thiophenes under
optimized conditions
This method Reported method [Ref.]
Time Yield
(min) (%)
Time
(min)
Yield
(%)
Entry
Ar
Phenyl
Phenyl
Phenyl
4-Chlorophenyl 4-Chlorophenyl
R
7a
7b
7c
7d
7e
7f
Phenyl
7
7
7
7
7
7
89
84
87
72
65
62
180
180
180
180
30
98[12]
56[12]
56[9]
66[9]
82[15]
—
4-Bromophenyl
4-Chlorophenyl
Phenyl
4-Biphenyl
Ethoxy
Ethoxy
—
(30 m ꢁ 0.25 mm ꢁ 0.2 lml MSD: HP5793) was used to record the mass
spectra. The microwave-assisted reactions were performed in a micro-
wave laboratory reactor (Ethos MR).
Scheme 3. Proposed mechanism.

2-Amino-3-aryl-5-Substituted Thiophenes
2049
Scheme 4. Trapping of iminium ion I with water.
Preparation of Catalyst
The KF-Al2O3 support was prepared according to previously reported
procedure[25] with some modification. A mixture of potassium fluoride
(45 g) and basic alumina (55 g, type T, Merck) in water (100 ml) was stir-
red at room temperature for 10 min. The resulting suspension was con-
centrated in vacuum and dried in a vacuum oven at 120 ꢀC for 15 h.
Use of basic alumina in the solid support gave better results relative to
the neutral one.
Procedure for Preparation of 2-Amino-3-aryl-5-substituted Thiophenes
under Microwave Heating
To an equimolar mixture of 3 (Ar: phenyl) and 4 (Ar: 3-methylphenyl),
KF-Al2O3 (0.25 g) was added, and then the mixture was heated in a
microwave oven for 7 min. After cooling, the residue was subjected to col-
umn chromatography (EtOAc=hexane 1:4) on silica gel to obtain pure
products.
Spectra Data of the Selected Products
Compound 6a: 5-Morpholin-4-yl-4-phenyl-thiophene-2-carboxylic
Acid m-Tolylamide
1H NMR (CDCl3, 500 MHz) d (ppm): 7.70 (d, J ¼ 7.22 Hz, 2H), 7.63 (s,
1H), 7.61 (s, 1H), 7.50 (m, 1H), 7.41–7.45 (m, 3H), 7.33 (d, J ¼ 7.4 Hz,
1H), 7.26 (t, J ¼ 7.8 Hz, 1H), 6.98 (d, J ¼ 7.4 Hz, 1H), 3.80 (t, J ¼ 4.6 Hz,
4H), 3.03 (t, J ¼ 4.6 Hz, 4H), 2.39 (s, 3H); 13C NMR (CDCl3, 125 MHz)
d (ppm): 160.42, 158.65, 139.41, 138.22, 135.92, 131.13, 129.30, 129.13,
128.06, 127.57, 127.38, 127.20, 125.51, 121.10, 117.50, 66.84, 52.81,
21.92; MS (EI) m=z: 378 (Mþ).

2050
H. Saeidian et al.
Compound 6b: 5-Morpholin-4-yl-4-phenyl-thiophene-2-carboxylic
Acid (4-Chloro-phenyl)-amide
1H NMR (CDCl3, 500 MHz) d (ppm): 7.73 (s, 1H), 7.68 (d, J ¼ 7.53 Hz,
2H), 7.58–7.61 (m, 3H), 7.43 (t, J ¼ 7.57 Hz, 2H), 7.32–7.34 (m, 3H), 3.78
(t, J ¼ 4.6 Hz, 4H), 3.02 (t, J ¼ 4.6 Hz, 4H); 13C NMR (CDCl3,
125 MHz) d (ppm): 160.97, 158.85, 138.03, 136.10, 131.73, 128.96,
128.93, 128.57, 127.87, 127.69, 127.33, 126.85, 121.82, 66.68, 52.69; MS
(EI) m=z: 398 (Mþ).
Compound 6c: 5-Morpholin-4-yl-4-phenyl-thiophene-2-carboxylic
Acid Naphthalene-1-ylamide
1H NMR (CDCl3, 500 MHz) d (ppm): 8.21 (s, 1H), 7.88–7.95 (m, 3H),
7.70–7.74 (m, 4H), 7.42–7.53 (m, 5H), 7.33 (d, J ¼ 7.4 Hz, 1H), 3.80 (t,
J ¼ 4.6 Hz, 4H), 3.02 (t, J ¼ 4.6 Hz, 4H); 13C NMR (CDCl3, 125 MHz)
d (ppm): 161.33, 158.75, 135.95, 134.57, 132.73, 131.73, 129.14, 129.12,
128.10, 128.03, 127.57, 127.39, 126.83, 126.72, 126.43, 126.41, 126.15,
121.93, 121.41, 66.85, 52.80; MS (EI) m=z: 414 (Mþ).
Compound 7b: (4-Bromo-phenyl)-(5-morpholin-4-yl-4-phenyl-
thiophene-2-yl)-methanone
1H NMR (CDCl3, 500 MHz) d (ppm): 7.73 (d, J ¼ 8.26 Hz, 2H), 7.65 (d,
J ¼ 8.28 Hz, 2H), 7.59 (d, J ¼ 7.54 Hz, 2H), 7.53 (s, 1H), 7.43 (t,
J ¼ 7.57, 2H), 7.32 (t, J ¼ 8.34 Hz, 1H), 3.80 (t, J ¼ 4.6 Hz, 4H), 3.12
(t, J ¼ 4.6 Hz, 4H); 13C NMR (CDCl3, 125 MHz) d (ppm): 186.42,
163.34, 139.22, 137.56, 135.97, 132.7, 130.81, 130.52, 129.23, 128.14,
127.78, 126.80, 126.68, 66.60, 52.24; MS (EI) m=z: 428 (Mþ).
Compound 7f: 4-Biphenyl-4-yl-5-morpholin-4-yl-thiophene-
2-carboxylic Acid Ethyl Ester
1H NMR (CDCl3, 500 MHz) d (ppm): 7.84 (s, 1H), 7.78 (d, J ¼ 8.14 Hz,
2H), 7.65–7.67 (m, 4H), 7.48 (t, J ¼ 7.55 Hz, 2H), 7.38 (t, J ¼ 7.29 Hz,
1H), 4.38 (q, J ¼ 7.1 Hz, 2H), 3.81 (t, J ¼ 4.6 Hz, 4H), 3.07 (t, J ¼ 4.6 Hz,
4H), 1.43 (t, J ¼ 7.1 Hz, 3H); 13C NMR (CDC13, 125 MHz) d (ppm):
162.58, 159.91, 140.92, 140.21, 136.04, 134.90, 129.23, 128.31, 127.81,
127.67, 127.34, 126.78, 121.88, 66.78, 61.15, 52.74, 14.95; MS (EI) m=z:
393 (Mþ).

2-Amino-3-aryl-5-Substituted Thiophenes
2051
Compound 8: 4-(1-Benzylsulfanyl-2-phenyl-buta-1,3-dienyl)-
morpholine
1H NMR (CDCl3, 500 MHz) d (ppm): 9.96 (s, 1H), 7.36–7.32 (m, 5H),
7.28 (d, J ¼ 9.8 Hz, 2H), 7.23 (t, J ¼ 7.41 Hz, 1H), 7.01 (d, J ¼ 7.33 Hz,
2H), 3.96 (s, 2H), 3.56 (t, J ¼ 4.68 Hz, 4H), 3.13 (t, J ¼ 4.68 Hz, 4H);
13C NMR (CDCl3, 125 MHz) d (ppm): 189.91, 167.39, 137.04, 136.93,
130.73, 129.25, 129.16 128.71, 128.22, 127.17, 122.14, 66.77, 52.71,
40.36; MS (EI) m=z: 339 (Mþ).
ACKNOWLEDGMENT
We acknowledge the Islamic Development Bank (IDB) for granting a
loan in 1993 for purchasing a 500-MHz Bruker NMR spectrometer.
REFERENCES
1. Loupy, A. Microwaves in Organic Synthesis; John Wiley-VCH: New York,
2002.
2. Habibi, D.; Marvi, O. Montmorillonite KSF clay as an efficient catalyst for
the synthesis of 1,4-dioxo-3,4-dihydrophthalazine-2(1H)-carboxamides and
-carbothioamides under solvent-free conditions using microwave irradiation.
Catal. Commun. 2007, 8, 127.
3. Bengtson, A.; Hallberg, A.; Larhed, M. Fast synthesis of aryl triflates with
controlled microwave heating. Org. Lett. 2002, 4, 1231.
4. Xu, L. W.; Xia, C. G.; Li, J. W.; Li, F. W.; Zhou, S. L. Efficient palladium=
copper cocatalyzed C-N coupling reaction of unactivated aryl bromide
or iodide with amino acid under microwave heating. Catal. Commun. 2004,
5, 121.
5. Gold, H.; Ax, A.; Vrang, L.; Samuelsson, B.; Karlen, A.; Hallberg, A.;
Larhed, K. M.; Anders, H.; Mats, L. Fast and selective synthesis of novel
cyclic sulfamide HIV-1 protease inhibitors under controlled microwave heat-
ing. Tetrahedron 2006, 62, 4671.
6. Yadav, G. D.; Desai, N. M. Novelties of low energy microwave irradiation in
`
tri-phase vis-a-vis bi-liquid phase-transfer catalysis in selective etherification
of aromatic phenols. Catal. Commun. 2006, 7, 325.
7. Bougrin, K.; Loupy, A.; Soufiaoui, M. Microwave-assisted solvent-free
heterocyclic synthesis. J. Photochem. Photobio. C. 2005, 6, 139.
8. Moghaddam, M. F.; Zali- Boinee, H. An efficient and facile one-step
synthesis of highly substituted thiophenes. Tetrahedron 2004, 60, 6085.
9. Pillai, A. D.; Rathod, P. D.; Xavier, F. P.; Vasu, K. K.; Padh, H.;
Sudarsanam, V. Design synthesis and pharmacological evaluation of some

2052
H. Saeidian et al.
2-[4-morpholino]-5-substituted thiophenes as novel anti-inflammtory agents;
generation of a novel anti-inflammatory pharmacophore. Bio. Med. Chem.
2004, 12, 4667.
10. Leban, J.; Kralik, M.; Mies, J.; Baumgartner, R.; Gassen, M.; Tasler, S.
Biphenyl-4-ylcarbamoyl thiophene carboxylic acids as potent DHODH
inhibitors. Bio. Med. Chem. 2006, 16, 267.
11. Rothemunt, P. A new Porphyrin synthesis. The synthesis of Porphin. J. Am.
Chem. Soc. 1936, 58, 625.
12. Noack, A.; Hartman, H. Synthesis and characterisation of N,N-disubstituted
2-amino-5-acylthiophenes and 2-amino-5-acylthiazoles. Tetrahedron 2002,
58, 2137.
13. Gewald, K.; Schinke, E.; Bottcher, H. Heterocyclen aus CH-aciden
Nitrilen, VIII. 2-Amino-thiophene aus methylenaktiven Nitrilen, Carbonyl-
verbindungen und Schewefel. Chem. Ber. 1966, 99, 94.
14. Pinto, I. L.; Jarvest, R. L.; Serafinowska, H. T. The synthesis of 5-alkoxy and
5-amino substituted thiophenes. Tetrahedron Lett. 2000, 41, 1597.
15. Heyde, C.; Zug, I.; Hartmann, H. A simple route to N,N-dialkyl derivatives
of 2-amino-5-thiophenecarboxylates. Eur. J. Org. Chem. 2000, 3273.
16. Moghaddam, M. F.; Saeidian, H. Controlled microwave-assisted synthesis of
ZnO nanopowder and its catalytic activity for O-acylation of alcohol and
phenol. Mater. Sci. Eng. B. 2007, 139, 265.
17. Mirjafary, Z.; Saeidian, H.; Sadeghi, A.; Moghaddam, M. F. ZnO nano-
particles: An efficient nanocatalyst for the synthesis of b-acetamido ketones=
esters via a multi-component reaction. Catal. Commun. 2008, 9, 299.
18. Moghaddam, M. F.; Zali-Boinee, H. Oxidative cyclization of thiobenzani-
lides to benzothiazoles using N-benzyl-DABCO tribromide under mild
conditions. Synlett 2005, 1612.
19. Moghaddam, M. F.; Zali-Boinee, H. A versatile one-pot synthesis of
2,3,5-tri-substituted thiohenes from thiomorpholides. Tetrahedron Lett.
2003, 44, 6253.
20. Moghaddam, M. F.; Dekamin, M. G. Thia-Fries rearrangement of aryl
sulfonates in dry media under microwave activation. Tetrahedron Lett.
2000, 41, 3479.
21. Moghaddam, M. F.; Porkaleh, H.; Zali-Boinee, H. Facile Double fries
rearrangement of diesters under microwave irradiation; application to the
synthesis of a biogenetically rare type of natural phenol. Lett. Org. Chem.
2006, 3, 123.
22. Moghaddam, M. F.; Ghafarzadeh, H. Microwave- assisted rapid hydro-
lysis and preparation of thioamides by Wilgerodt-Kindler reaction. Synth.
Commun. 2001, 31, 317.
23. Moghaddam, M. F.; Saeidian, H.; Mirjafary, Z.; Sadeghi, A. KF-Al203
promoted synthesis of fully substituted new indeno- and naphtho-fused
thiophenes under solvent-free conditions by controlled microwave heating.
Lett. Org. Chem. 2007, 4, 576.
24. Moghaddam, M. F.; Oskoui, A. A.; Zali-Boinee, H. Rapid and selective
acetalization of aldeheydes using anhydrous copper sulfate supported on

2-Amino-3-aryl-5-Substituted Thiophenes
2053
silica gel (CuSO4=SiO2) under microwave irradiation in solvent-free
conditions. Lett. Org. Chem. 2005, 2, 151.
25. Schmittiling, A. E.; Sawyer, J. S. Selective desilylation of tert-butyldimethyl-
silyl ethers of phenols using potassium fluoride-alumina and ultrasound.
Tetrahedron Lett. 1991, 32, 7207.