Michael addition reaction of thioacetic acid (AcSH) to conjugated alkenes under solvent- and catalyst-free conditions

Article abstract of DOI:10.1080/10426500903496713

A new and convenient procedure has been developed for the Michael addition reaction of thioacetic acid (AcSH) to a variety of conjugated alkenes under solvent- and catalyst-free conditions. These reactions proceeded in 5-60 min and produced the desired products in good to high yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500903496713

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Phosphorus, Sulfur, and Silicon and the
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Michael Addition Reaction of Thioacetic
Acid (AcSH) to Conjugated Alkenes
Under Solvent- and Catalyst-Free
Conditions
Sara Sobhani a & Soodabeh Rezazadeh a
a Department of Chemistry, College of Sciences, Birjand University,
Birjand, Iran
Version of record first published: 24 Sep 2010.
To cite this article: Sara Sobhani & Soodabeh Rezazadeh (2010): Michael Addition Reaction of
Thioacetic Acid (AcSH) to Conjugated Alkenes Under Solvent- and Catalyst-Free Conditions,
Phosphorus, Sulfur, and Silicon and the Related Elements, 185:10, 2076-2084
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Phosphorus, Sulfur, and Silicon, 185:2076–2084, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903496713
MICHAEL ADDITION REACTION OF THIOACETIC ACID
(AcSH) TO CONJUGATED ALKENES UNDER SOLVENT-
AND CATALYST-FREE CONDITIONS
Sara Sobhani and Soodabeh Rezazadeh
Department of Chemistry, College of Sciences, Birjand University, Birjand, Iran
A new and convenient procedure has been developed for the Michael addition reaction of
thioacetic acid (AcSH) to a variety of conjugated alkenes under solvent- and catalyst-free
conditions. These reactions proceeded in 5–60 min and produced the desired products in
good to high yields.
Keywords Catalyst-free; conjugated alkenes; Michael addition; solvent-free; thioacetic acid
INTRODUCTION
The thia-Michael addition is one of the most versatile and practical reactions for
C S bond formation in organic synthesis.1 The conversion of α,β-unsaturated carbonyl
compounds to the corresponding β-sulfido carbonyl derivatives provides a strategy for
the chemoselective protection of olefinic double bonds.2 In addition, these compounds
are starting materials for the generation of β-acylvinyl cations3 and homoenolate anion
equivalents.4 For these and other reasons, the thia-Michael addition is an important reaction
in organic synthesis and plays a critical role in biosynthesis and the synthesis of bioactive
compounds.5 To date, a great deal of effort has been directed toward the use of strong
nucleophilic thiols such as alkyl and aryl thiols as Michael donors in the Michael addition
reaction.6,7 Generally, harsh reaction conditions are required for the conversion of the newly
formed C S bond to more a synthetically versatile SH group.8 On the other hand, the use
of thioacids (RCOSH) as nucleophiles for the Michael addition reaction is more attractive,
since the resulting thioesters can be readily transformed into a SH group under various mild
reaction conditions.8 A literature survey indicates that in contrast to the existing methods for
the Michael addition of alkyl and aryl thiols to enones, few methods are known for the use of
thioacids as Michael donors.9–14 However, the reported procedures suffer from at least one
of the following drawbacks such as low yields of the products,9 use of toxic solvents,9,10
and long reaction times.9–11 Piperidine11 and diethylamine12 have been reported as the
common basic catalysts for conjugate addition of thioacetic acid (AcSH) to the enones.
These methods suffer from usually low yields and long reaction times (18–24 h). SnCl4 is
a Lewis acid catalyst that was used to achieve this kind of Michael addition reaction. In
this method, the product was isolated in a very low yield (8%) after a long reaction time
(68 h).10 Therefore, it is necessary to develop an efficient and convenient method for the
thia-Michael addition reaction of AcSH to conjugated alkenes.
Received 5 August 2009; accepted 18 November 2009.
Address correspondence to Sara Sobhani, Department of Chemistry, College of Sciences, Birjand University,
Birjand 414, Iran. E-mail: sobhanisara@yahoo.com
2076

MICHAEL ADDITION REACTION OF THIOACETIC ACID
2077
Table I Optimization of the Michael addition reaction of AcSH to 4-phenylbut-3-en-2-one
Conjugated
alkene:AcSH
Temperature
(◦C)
Time
(h)
Yielda
(%)
Entry
Solvent
1
2
3
4
5
6
7
8
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:2
rt
50
80
rt
rt
rt
—
—
—
Et2O
CHCl3
CH2Cl2
Toluene
—
24
24
24
24
24
24
24
1
40
50
50
50
5
20
10
85
rt
rt
aIsolated yield.
From both economic and environmental viewpoints, organic reactions under solvent-
and catalyst-free conditions have gained popularity in recent years. This is because solvent-
and catalyst-free reactions are greener and eliminate waste. Solvent-free reactions are
generally fast and give higher selectivity and yields, which may offer advantages over those
occurring in organic solvents.15
As a part of our research aimed at developing green chemistry by using water as the
reaction medium or by performing organic transformations under solvent-free conditions,16
in this article we describe a highly efficient, simple, and eco-friendly method for the Michael
addition reaction of AcSH to different conjugated alkenes without the use of catalyst or
solvent.
RESULTS AND DISSCUSION
In order to find the best reaction conditions, the Michael addition reaction of AcSH
to 4-phenylbut-3-en-2-one was studied as a model reaction under solvent-free conditions
at the temperature range of 25◦C to 80◦C. It was found that the temperature change did
not show a strong effect on the reaction yield, and the desired product was formed in only
40–50% yields after 24 h (Table I, entries 1–3). Then, a similar reaction was studied in
different solvents at room temperature, and again the product was obtained in low yields
(Table I, entries 4–7). The best result was found when the reaction was performed in the
presence of an excess amount of AcSH under solvent-free conditions at room temperature
(Table I, entry 8).
With optimal conditions in hand, we examined the generality of this procedure by
the reaction of different conjugated alkenes with AcSH (Scheme 1, Table II).
SAc
X
Catalyst-Free
Solvent-Free
X
AcSH
R
+
R
Y
Y
1-13
R=H, aryl, heteroaryl
X=C(O)R' [R'=alkyl, aryl, alkoxy], NO2
Y=H, Me, CO2Et
Scheme 1

2078
S. SOBHANI AND S. REZAZADEH
Table II Michael addition reaction of AcSHa to conjugated alkenes under solvent- and catalyst-free conditions
Entryb
1
Conjugated alkenes
Productref
Time (min)
60
Yieldc (%)
85
113
2
3
213
5
5
93
98
313
4
5
413
5
5
90
85
5
6
6
5
98
7
8
7
8
5
95
97
15
9d
9
5
97
85
10
10
30
(Continued on next page)

MICHAEL ADDITION REACTION OF THIOACETIC ACID
2079
Table II Michael addition reaction of AcSHa to conjugated alkenes under solvent- and catalyst-free conditions
(Continued )
Entryb
11
Conjugated alkenes
Productref
Time (min)
15
Yieldc (%)
75
11
12
13
12
5
5
76
98
1314
aConditions: AcSH (2 equiv.).
bConditions: room temperature (except for entry 10).
cIsolated yields.
dConditions: 50◦C.
As it is indicated in Table II, chalcone derivatives carrying either an electron-donating
or an electron-withdrawing substitute reacted in short reaction times to give the desired
products in high yields (entries 2–6). Heterocyclic systems (e.g., thiophene and furan, Table
II, entries 7–9) were also effective substrates to successfully execute Michael addition reac-
tions under the similar reaction conditions. In all of these reactions, no byproducts resulting
from the undesired 1,2-addition and/or bis-addition reaction were observed. In addition to
α,β-unsaturated ketones, some other conjugated alkenes were also screened to carry out the
conjugate addition by AcSH under solvent-free conditions. For α,β-unsaturated malonate,
esters, and nitro compound, the reaction worked well and the expected products (10–13)
were obtained in 75–98% yields (Table II, entries 10–13). The Michael addition reaction
of AcSH to cinnamaldehyde produced the desired product with low yield (40%) due to the
formation of a byproduct resulting from 1,2-addition reaction of AcSH to carbonyl group.
In order to show the advantages of the present work in comparison with other re-
ported protocols, we compared the reaction conditions of this method with those reported
previously (Table III).
As shown in Table III, the reported procedures for the catalyst-free Michael addition
reaction of AcSH to conjugated alkenes required long reaction times to produce the desired
products in low to moderate yields (entries 2–4). The reaction resulted in the Michael
addition product in good to high yields in the presence of chiral catalysts, but in low
to moderate ee, probably due to the catalyst-free Michael addition reaction (background
reaction) (Table III, entries 5 and 6).
In conclusion, we have introduced an experimentally simple and convenient process
for the Michael addition reaction of AcSH to a variety of Michael acceptors under solvent-
and catalyst-free conditions. Short reaction times, good to high yields, no side product
formation, and simple extractive work-up make this method an attractive and a useful
contribution to the present methodologies.
EXPRIMENTAL
Chemicals were purchased from Merck and Fluka Chemical Companies. IR spectra
were run on a Perkin Elmer 780 instrument. NMR spectra were recorded on a Bruker

2080

2081

2082
S. SOBHANI AND S. REZAZADEH
Avance DPX-250. Mass spectra were recorded on a Shimadzu GCMS-QP5050A. The
purity of the products and the progress of the reactions were accomplished by TLC on
silica-gel polygram SILG/UV254 plates. Elemental analysis for C and H were obtained
using a Heraeus CHN-O-Rapid analyzer.
General Procedure for the Michael Addition Reaction of AcSH
to Conjugated Alkenes
A mixture of conjugated alkene (1 mmol) and AcSH (2 mmol) was stirred for an
appropriate time at room temperature or at 50◦C (Table I). Then ethyl acetate (2 mL) was
added to the reaction mixture, and the pure product was isolated from this mixture by plate
chromatography eluted with n-hexane:EtOAc (10–5:1).
Spectral Data for Selected Products
1
Thioacetic acid S-[1-(4-nitro-phenyl)-3-oxo-3-phenyl-propyl) ester (5). H
NMR (CDCl3, TMS): δ 2.33 (s, 3 H), 3.62–3.81 (m, 2 H), 5.20 (t, 1 H, J = 6.5 Hz), 7.23–7.32
(m, 5 H), 8.08 (d, 2 H, J = 8.8 Hz), 8.30 (d, 2 H, J = 8.8 Hz) ppm; 13C NMR (CDCl3, TMS):
δ 30.4, 43.5, 45.3, 123.9, 127.7, 128.8, 129.2, 139.6, 140.7, 146.8, 150.4, 194.6, 195.1 ppm;
IR (neat): ν 1685, 1662 (CO) cm−1; MS (70 eV), m/e: 330 (M++1), 150 (100%). Anal.
Calcd. for C17H15NO4S: C, 61.99; H, 4.59. Found: C, 61.98; H, 4.57%.
Thioacetic acid S-[1-(4-methyl-phenyl)-3-oxo-3-phenyl-propyl) ester (6).
1H NMR (CDCl3, TMS): δ 2.31 (s, 6 H), 3.64–3.71 (m, 2 H), 5.28 (t, 1 H, J = 7.8 Hz),
7.12 (d, 2 H, J = 8.0 Hz), 7.29 (d, 2 H, J = 7.8 Hz), 7.45 (t, 2 H, J = 7.5 Hz), 7.56 (t, 1
H, J = 6.8 Hz), 7.96 (d. 2 H, J = 8.3 Hz) ppm; 13C NMR (CDCl3, TMS): δ 21.2, 30.4,
43.3, 44.6, 127.6, 128.2, 128.6, 129.4, 133.3, 136.5, 137.2, 137.5, 194.7, 196.5 ppm; IR
(neat): ν 1679, 1671 (CO) cm−1; MS (70 eV), m/e: 298 (M+), 105 (100%). Anal. Calcd for
C18H18O2S: C, 72.54; H, 6.08. Found: C: 72.52; H, 6.05%.
1
Thioacetic acid S-[1-(furan-2-yl)-3-oxo-butyl) ester (7). H NMR (CDCl3,
TMS): δ 2.11 (s, 3 H), 2.27 (s, 3 H), 3.00 (dd, 1 H, J = 17.3 Hz, J = 6.3 Hz), 3.15 (dd, 1
H, J = 17.0 Hz, J = 8.3 Hz), 5.14 (t, 1 H, J = 7.8 Hz), 6.17 (s, 1 H), 6.23 (s, 1 H), 7.24 (s,
1 H) ppm; 13C NMR (CDCl3, TMS): δ 29.9, 30.3, 36.1, 46.6, 107.1, 110.5, 142.0, 152.4,
193.9, 204.4 ppm; IR (neat): ν 1677, 1681 (CO) cm−1; MS (70 eV), m/e: 212 (M+), 137
(100%). Anal. Calcd for C10H12O3S: C, 56.58; H, 5.70. Found: C, 56.58; H, 5.69%.
1
Thioacetic acid S-[1-(furan-2-yl)-3-oxo-3-phenyl-propyl] ester (8). H
NMR (CDCl3, TMS): δ 2.32 (s, 3 H), 3.62 (dd, 1 H, J = 17.3 Hz, J = 6.0 Hz), 3.73 (dd, 1
H, J = 17.3 Hz, J = 8.0 Hz), 5.39 (t, 1 H, J = 7.8 Hz), 6.25 (s, 2 H), 7.29 (s, 1 H), 7.45
(t, 2 H, J = 7.3 Hz), 7.56 (t, 1 H, J = 7 Hz), 7.95 (d, 2 H, J = 7.3 Hz) ppm; 13C NMR
(CDCl3, TMS): δ 30.4, 36.6, 42.0, 107.2, 110.6, 128.1, 128.7, 133.4, 136.3, 142.0, 152.6,
194.1, 195.9 ppm; IR (neat): ν 1677 (CO) cm−1; MS (70 eV), m/e: 274 (M+), 105 (100%).
Anal. Calcd for C15H14O3S: C, 56.67; H, 5.14. Found: C, 56.66; H, 5.12%.
1
Thioacetic acid S-[1-(thiophen-2-yl)-3-oxo-3-phenyl-propyl] ester (9). H
NMR (CDCl3, TMS): δ 2.32 (s, 3 H), 3.73 (d, 2 H, J = 6.5 Hz), 5.58 (t, 1 H, J = 7 Hz)
6.88 (t, 1 H, J = 3.8 Hz), 7.03 (d, 1 H, J = 3.3 Hz), 7.15 (d, 1 H, J = 5.3 Hz), 7.46 (t, 2 H,
J = 7.3 Hz), 7.57 (t, 1 H, J = 7.3 Hz), 7.95 (d, 2 H, J = 7.5 Hz) ppm; 13C NMR (CDCl3,
TMS): δ 30.3, 38.6, 45.3, 124.8, 125.7, 126.7, 128.1, 128.7, 133.4, 136.4, 144.0, 194.3,

MICHAEL ADDITION REACTION OF THIOACETIC ACID
2083
195.9 ppm; IR (neat): ν 1671 (CO) cm−1; MS (70 eV), m/e: 290 (M+), 105 (100%). Anal.
Calcd for C15H14O2S2: C, 62.04; H, 4.86. Found: C, 62.02; H, 4.84%.
1
Diethyl 2-(acetylthio(phenyl)methyl)malonate (10). H NMR (CDCl3,
TMS): δ 1.02 (t, 3 H, J = 7.0 Hz), 1.22 (t, 3 H, J = 7.0 Hz), 2.24 (s, 3 H), 3.94–4.02 (m,
3 H), 4.17 (q, 2 H, J = 7.0 Hz), 5.31 (d, 1 H, J = 10 Hz), 7.18–7.35 (m, 5 H) ppm; 13C
NMR (CDCl3, TMS): δ 13.7, 13.9, 30.3, 45.9, 57.1, 61.7, 61.8, 127.8, 128.1, 128.5, 128.8,
139.3, 166.3, 166.8, 192.7 ppm; IR (neat): ν 1722, 1718, 1686 (CO) cm−1; MS (70 eV),
m/e: 325 (M++1), 249 (100%). Anal. Calcd for C16H20O5S: C, 59.24; H, 6.21. Found: C,
59.21; H, 6.19%.
1
Methyl 3-(acetylthio)propanoate (11). H NMR (CDCl3, TMS): δ 2.31 (s, 3
H), 2.61 (t, 2 H, J = 7.0 Hz), 3.08 (t, 2 H, J = 7.0 Hz), 3.67 (s, 3 H) ppm; 13C NMR
(CDCl3, TMS): δ 24.2, 30.5, 34.1, 51.8, 172.1, 195.5 ppm; IR (neat): ν 1688 (CO) cm−1
;
MS (70 eV), m/e: 162 (M+), 43 (100%). Anal. Calcd for C6H10O3S: C, 44.43; H, 6.21.
Found: C, 44.42; H, 6.18%.
1
Butyl 3-(acetylthio)propanoate (12). H NMR (CDCl3, TMS): δ 0.90 (t, 3 H,
J = 7.3 Hz), 1.28–1.42 (m, 2 H), 1.52–1.67 (m, 2 H), 2.31 (s, 3 H), 2.59 (t, 2 H, J =
7.0 Hz), 3.08 (t, 2 H, J = 7.0 Hz), 4.06 (t, 2 H, J = 6.8 Hz) ppm; 13C NMR (CDCl3, TMS):
δ 13.7, 19.0, 24.2, 30.5, 34.3, 64.6, 171.7, 195.6 ppm; IR (neat): ν 1678, 1685 (CO) cm−1
;
MS (70 eV), m/e: 204 (M+), 43 (100%). Anal. Calcd for C9H16O3S: C, 52.91; H, 7.89.
Found: C, 52.87; H, 7.85%.
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