KF/Al2O3-mediated Michael addition of thiols to electron-deficient olefins

Article abstract of DOI:10.1080/00397910500189783

Potassium fluoride supported on alumina efficiently catalyzes Michael addition of aromatic and aliphatic thiols to a variety of conjugated alkenes such as α,β-unsaturated carbonyl compounds, carboxylic esters, amides, nitriles and chalcones. The Michael adducts are produced in good to excellent yields and relatively in short times. The catalyst can be recycled for subsequent reactions without any appreciable loss of efficiency. Copyright Taylor & Francis, Inc.

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KF/Al2O3-Mediated Michael
Addition of Thiols to
Electron‐Deficient Olefins
F. Matloubi Moghaddam a , G. Rezanejade Bardajee a
& R. Oftadeh Chadorneshine Veranlou a
a Sharif University of Technology, Department of
Chemistry , Tehran, Iran
Published online: 18 Aug 2006.
To cite this article: F. Matloubi Moghaddam , G. Rezanejade Bardajee & R. Oftadeh
Chadorneshine Veranlou (2005) KF/Al2O3-Mediated Michael Addition of Thiols to
Electron‐Deficient Olefins, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 35:18, 2427-2433
To link to this article: http://dx.doi.org/10.1080/00397910500189783
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Synthetic Communicationsw, 35: 2427–2433, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500189783
KF/Al2O3-Mediated Michael Addition
of Thiols to Electron-Deficient Olefins
F. Matloubi Moghaddam, G. Rezanejade Bardajee,
and R. Oftadeh Chadorneshine Veranlou
Sharif University of Technology, Department of Chemistry, Tehran, Iran
Abstract: Potassium fluoride supported on alumina efficiently catalyzes Michael
addition of aromatic and aliphatic thiols to a variety of conjugated alkenes such as
a,b-unsaturated carbonyl compounds, carboxylic esters, amides, nitriles and
chalcones. The Michael adducts are produced in good to excellent yields and relatively
in short times. The catalyst can be recycled for subsequent reactions without any
appreciable loss of efficiency.
Keywords: Electron-deficient olefins, KF/Al2O3, Michael addition, thiols
INTRODUCTION
The 1,4-addition of thiols to electron-deficient olefins to form a carbon–sulfur
bond constitutes a key reaction in biosynthesis as well as in synthetic organic
chemistry. Usually this conjugate addition is based either on the activation of
thiols by base or activation of the acceptor olefins with Lewis acids.[1,2]
Recently various ionic liquid–catalyzed conjugate additions of thiols
have also been reported in the literature.[3–6] Expensive reagents, harsh
reaction conditions, uncommon reagents, long reaction times, side reactions,
and difficult workup are major disadvantages of the reported methods.
Received in the U.K. January 11, 2005
Address correspondence to F. Matloubi Moghaddam, Sharif University of
Technology, Department of Chemistry, P.O. Box 11365-9516, Tehran, Iran. E-mail:
matloubi@sharif.edu
2427

2428
F. M. Moghaddam, G. R. Bardajee, and R. O. C. Veranlou
Scheme 1.
We report here an efficient conjugate addition of thiols to some activated
alkenes in the presence of potassium fluoride supported on alumina[7] as a base
(Scheme 1).
RESULTS AND DISCUSSION
Our investigations showed that aromatic and aliphatic thiols react smoothly
with various conjugated alkenes in the presence of KF/Al2O3. The corres-
ponding 1,4-adducts were obtained in high to excellent yields. To obtain the
optimized reaction condition, different types of solvents as well as solvent-
free conditions were examined. Acetonitrile, dichloromethane, and diethyl
ether were found to be suitable for this reaction. The results are summarized
in Table 1. Because of its high yields and shorter reaction times, acetonitrile
was found to be the best solvent for this reaction. Solvent-free conditions also
gave good results (Entries 4, 8, 13, Table 1). Most of these reactions proceeded
at 45–558C in relatively short time periods, and pure products were obtained
by crystallization or PTLC. In the case of acrylonitrile and metaacrylonitrile,
the reaction was accomplished at room temperature. The results of optimized
conditions are shown in Table 2. Aliphatic thiols such as n-butylmercaptane
and benzylmercaptane reacted faster than thiophenol (Entries 1–7, Table 2).
It has also been observed that the reaction is greatly influenced by the b-sub-
stitution of the conjugated alkene; that is, b-substituted conjugated olefins
react slower than the nonsubstituted alkenes on the b-position (Entries 6,
13, Table 2). The aryl substituent in b-position in particular has more pro-
nounced effect on retarding the reaction (Entries 6, 12, 13, Table 2). In
contrast, acrylonitrile and metaacrylonitrile reacted in almost the same
manner (Entries 1, 15, Table 2). In the case of dibenzylideneacetone, a bis-
1,4-adduct of thiols were observed under the optimized reaction conditions
(Entries 18, 19, Table 2). The Michael addition of thiophenols to
acrylamide and metaacrylamide have also been studied and afforded high
yields (Entries 16, 17, Table 2). In conclusion, KF/Al2O3 has shown to be
an efficient catalyst for the Michael addition of thiols to electron-deficient
olefins in good to excellent yields. The support is prepared conveniently
compared to other reported reagents. Also this support is nonvolatile, non-
flammable, ecofriendly, inexpensive, safe, clean, and recyclable.

KF/Al2O3-Mediated Michael Addition of Thiols
Table 1. Effect of solvent on thio-Michael addition
2429
Time
(min)
Yield
(%)
Entry
Electrophile
Nucleophile
PhSH
Solvent
Acetonitrile
1
2
3
4
15
25
30
30
92
86
70
90
PhSH
Dichloromethane
Diethylether
Solvent-free
PhSH
PhSH
5
6
7
8
9
PhSH
Acetonitrile
15
30
30
30
20
91
81
72
85
90
PhSH
Dichloromethane
Diethyl ether
Solvent-free
PhSH
PhSH
PhCH2SH
Diethyl ether
10
11
PhSH
PhSH
Acetonitrile
20
35
90
80
Dichloromethane
12
13
PhSH
PhSH
Diethyl ether
Solvent-free
45
30
80
82
EXPERIMENTAL
The compounds gave satisfactory spectroscopic data. IR spectra were taken
as thin films for liquid compounds and as KBr pellets for solids on a
Nicolet spectrometer (Magna 550). A bruker (DRX-500 Avance) NMR was

2430
F. M. Moghaddam, G. R. Bardajee, and R. O. C. Veranlou
Table 2. KF/Al2O3 mediated conjugate addition of thiols to electron-deficient olefins
Time Yield
(min) (%)a
Entry
1
Electrophile
Nucleophile
PhSH
Productb
15
10
95
98
2
3
n-BuSH
PhSH
15
10
91
98
4
5
n-BuSH
PhCH2SH
10
98
6
7
PhSH
20
10
90
93
n-BuSH
8
9
PhSH
20
15
20
91
92
90
n-BuSH
PhSH
10
11
12
n-BuSH
PhSH
15
50
95
80
(continued)

KF/Al2O3-Mediated Michael Addition of Thiols
Table 2. Continued
2431
Time Yield
(min) (%)a
Entry
13
Electrophile
Nucleophile
PhSH
Productb
40
60
20
30
30
85
80
95
85
85
14
15
16
17
PhSH
PhSH
PhSH
PhSH
18
19
PhSH
100
70
60
85
n-BuSH
aAll yields refer to isolated products.
1
bAll products were characterized by m p, IR, and HNMR, and their physical data
were similar to those reported in the literature.[3–5,9–14]
1
used to record the H NMR spectra. All NMR spectra were determined in
CDCl3 at ambient temperature. Melting points were determined on a Buchi
B540 apparatus.
Procedure for the Preparation of KF/Al2O3 Support
The KF/Al2O3 support was prepared according to the previously reported
procedure[8] with some modifications. A mixture of potassium fluoride
(45 g) and basic alumina (55 g, type T, Merck) in water (100 mL) was
stirred at room temperature for 10 min. The resulting suspension was concen-
trated in vacuo and dried in a vacuum oven at 1208C for 15 h. The use of
basic alumina in the solid support gave better results compared to the
neutral one.

2432
F. M. Moghaddam, G. R. Bardajee, and R. O. C. Veranlou
General Procedure for Michael Additions: Representative One
(Entry 7, Table 2)
To a suspension of KF/basic Al2O3 (600 mg) in acetonitrile (10 ml) n-buthyl-
mercaptane (91.1 mg, 1.01 mmol) was added and stirred at room temperature
for 5 min. Then, methylacrylate (86.1 mg, 1 mmol) was added to the mixture
and stirred at 45–558C for 10 min as indicated by TLC (ethyl acetate/
petroleum ether 1:4) for a complete reaction. After filtration of the catalyst,
the filtrate was washed with aqueous NaOH (8%), and the organic phase
was evaporated under reduced pressure to furnish methyl 3-thiobutylpropio-
nate as colorless oil. The crude product was sufficiently pure (TLC and
lH NMR) and more pure product (93%) was obtained by PTLC. IR 2956,
1
1741 cm21; H NMR (500 MHz, CDCl3) d 3.7 (s,3H), 2.78 (t, J ¼ 7.2 Hz,
2H), 2.61 (t, J ¼ 7.2 Hz, 2H), 2.53 (t, J ¼ 7.4 Hz, 2H), 1.62–1.52 (m, 2H),
1.47–1.37 (m, 2H), 0.92 (t, J ¼ 7.3 Hz, 3H); 13C NMR d 172.8, 52.1, 35.1,
32.2, 31.9, 27.3, 22.3, 14.0. The residual KF/Al2O3 support was dried
under vacuum at 1208C for 10 h and reused for subsequent reactions. No
loss of efficiency with regard to reaction time and yield was observed after
three uses.
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