Catalytic synthesis of α-Oxoketene S,S-acetals in a wet ionic liquid [Bmim]Cl/H2O homogeneous system

Article abstract of DOI:10.3390/molecules16064500

A clean, practical and environmentally friendly synthesis in a homogeneous system has been developed for α-oxoketene S,S-acetals. A mixture of [Bmim]Cl and water was used as medium. The best economical and practical molar ratio of [Bmim]Cl to substrate was 4 to 1. With various types of 1,3-dicarbonyl compounds as substrate, the corresponding α-oxoketene S,S-acetals have been prepared under mild reaction conditions with yields of 53-74% after purification with silica gel column. [Bmim]Cl/water can be recycled several times.

Full text of DOI:10.3390/molecules16064500

Molecules 2011, 16, 4500-4510; doi:10.3390/molecules16064500
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Catalytic Synthesis of α-Oxoketene S,S-Acetals in a Wet Ionic
Liquid [Bmim]Cl/H2O Homogeneous System
Ping Yu 1,2, Yuangang Zu 1,2,*, Yujie Fu 1,2,* and Thomas Efferth 3
1
Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University,
Harbin 150040, China
2
Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry
University, Harbin 150040, China
3
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of
Mainz, Mainz 55128, Germany
* Authors to whom correspondence should be addressed; E-Mails: zygorl@vip.hl.cn (Y.Z.);
yujie_fu2002@yahoo.com (Y.F.); Tel./Fax: +86-451-82190535.
Received: 23 March 2011; in revised form: 11 May 2011 / Accepted: 18 May 2011 /
Published: 27 May 2011
Abstract: A clean, practical and environmentally friendly synthesis in a homogeneous
system has been developed for α-oxoketene S,S-acetals. A mixture of [Bmim]Cl and water
was used as medium. The best economical and practical molar ratio of [Bmim]Cl to
substrate was 4 to 1. With various types of 1,3-dicarbonyl compounds as substrate, the
corresponding α-oxoketene S,S-acetals have been prepared under mild reaction conditions
with yields of 53–74% after purification with silica gel column. [Bmim]Cl/water can be
recycled several times.
Keywords: 1,3-dicarbonyl compounds; α-oxoketene S,S-acetals; [Bmim]Cl; water
1. Introduction
α-Oxoketene S,S-acetals are known as versatile intermediates for the preparation of various
functional groups such as acetylenes [1], substituted furans [2], thiophene derivatives [3] and highly
substituted phenols [4,5]. The synthesis of an α-oxoketene S,S-acetal albeit in low yield was first
reported by Kelber and co-workers in 1910 using potassium hydroxide as base [6]. In 1988, Choi et al.

Molecules 2011, 16
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[7] successfully prepared α-oxoketene S,S-acetals directly from ketones in good yields by choosing
potassium carbonate as weak base in N,N-dimethylformamide. However, environmental pollution and
post-processing difficulties of N,N-dimethylformamide led to some drawbacks. In 2005, Ouyang et al.
[8] successfully prepared α-oxoketene S,S-acetals in good yields using water as medium, and TBAB as
phase transfer catalyst in a solid-liquid system. However, uneven mixing is a frequent phenomenon in
solid-liquid systems, especially in the amplification reaction. In order to overcome this issue, we have
chosen ionic liquids as phase transfer catalyst [9] and cosolvent, water as medium to synthesize
α-oxoketene S,S-acetals. The most apparent advantage was that ionic liquids/H2O homogeneous
system could efficiently avoid uneven mixing of starting material mixtures. To the best of our
knowledge, the present investigation is the first report of such a synthesis method.
Ionic liquids had been generally studied as excellent solvents due to their unique physical and
chemical properties [10]. As an imidazolium ionic liquid, [Bmim]Cl has been widely used in many
reactions such as elimination reactions [11], one-pot synthesis of α-aminophosphonate derivatives
[12], oxidations [13,14], Friedel-Crafts acylations [15], methanolysis of polycarbonates [16],
S-methylation reactions [17] and Ferrier rearrangements [18]. Its clean, green, high yield, no vapor
pressure and recyclability characteristics were evidenced in these reactions. More interesting is the fact
that [Bmim]Cl in some reactions has the feature of decreasing the reaction temperature to room
temperature from 100–300 °C [19], promoting the reactivity of metal catalysts [20], greatly reducing
the reaction times [21], high selectivity [15,17,18] and less toxicity [17].
Water and ionic liquids mixtures were termed “wet ILs” [22] and are used as single-phase or
multi-phase systems. A wide range of applications have been realized in recent years such as
Knoevenagel condensation [23], Diels–Alder cycloadditions [24], synthesis of organophosphorus
compounds [25] and Biginelli-type reactions [26]. Some studies have indicated that the presence of
water has a great impact on ionic liquids [27,28]. These previous achievements encouraged us to
establish an environmentally friendly synthesis method for α-oxoketene S,S-acetals in an ionic
liquid/water system. The choice of ionic liquid, the ratio of ionic liquid to starting material, recycle
times and other factors were investigated and optimized to achieve a green, moderate yield synthesis of
α-oxoketene S,S-acetals.
2. Results and Discussion
2.1. Choice of Ionic Liquids
A weak alkaline system is needed for synthesis of α-oxoketene S,S-acetals rather than strong alkali
to prevent side reactions. Considering the extensive applications and especially the many favorable
features and its lower price [Bmim]Cl has been chosen for this investigation. Another frequently used
and cheap pyridine ionic liquid [Epy]BF4 has also been chosen for the investigation. The alkalinity was
regulated by addition of the weak base potassium carbonate. Water, the ionic liquids [Epy]BF4,
[Bmim]Cl, [Epy]BF4/water and different [Bmim]Cl/water ratios were used as solvents, respectively.
Results are shown in Table 1.

Molecules 2011, 16
Table 1. Reaction of 1a with carbon disulfide and 1,2-dibromoethane in ionic liquids/water
4502
under different conditions.
O
S
O
S
O
O
Ionic liquids/ H2O / K2CO3
N
H
N
H
CS2
BrCH2CH2Br (3)
1a
7a
Reaction
Medium
H2O
[EPy]BF4
Amount a
K2CO3
1a
(mmol)
Time b
(h)
20
20
20
15
5
5
5
5
8
Yield c
(%)
0
trace
trace
71
73
74
73
74
Entry
(mmol)/(mL)
15 (mL)
50 (mmol)
50 (mmol)
50/15
50/15
40/15
30/15
20/15
(mmol)
12.5
12.5
12.5
12.5
12.5
12.5
12.5
12.5
12.5
12.5
12.5
1
2
3
4
5
6
7
8
5
5
5
5
5
5
5
5
5
5
5
[Bmim]Cl
[EPy]BF4/H2O
[Bmim]Cl/H2O
[Bmim]Cl/H2O
[Bmim]Cl/H2O
[Bmim]Cl/H2O
[Bmim]Cl/H2O
[Bmim]Cl/H2O
[Bmim]Cl/H2O
Amount of reaction medium;
9
10/15
5/15
65
61
43
10
11
11
20
0.1/15
a
b
The reaction time was recorded after the addition of
1,2-dibromoethane; c Yields of 7a were obtained by purification with column chromatography.
No reaction product was detected when using water alone (Entry 1). When using [EPy]BF4,
[Bmim]Cl respectively, all materials appeared as a solid phase without further reactivity (Entry 2, 3),
indicating that the reaction did not take place in ionic liquids. However, under the systems of ionic
liquids [EPy]BF4, [Bmim]Cl and water (wet ILs), the reactions took place with good yields.
Acetoacetylaniline 5 mmol (taken as 1 equiv. relatively), potassium carbonate (2.5 equivs.), carbon
disulfide (1.2 equivs.) and 1,2-dibromoethane (1 equiv.) in [EPy]BF4/water (10 equivs./15 mL) led to
good reactivity and 71% yield (Entry 4). However, the reaction time took up to 15 hours. Then, the
reaction of acetylacetanilide (1 equiv.) in [Bmim]Cl/water (10 equivs./15 mL) was attempted in
accordance with the experimental procedures. Interestingly, a homogeneous system was obtained
giving 73% yield of product after 5 hours (Entry 5). It was reported that [Bmim]Cl plays an important
role in accelerating the reaction rate [18,21]. We assume that [Bmim]Cl also played the same role
in our reactions.
2.2. The Ratio of [Bmim]Cl to Substrate
To optimize the reaction conditions, several reactions were carried out changing the molar ratio
[Bmim]Cl to 1a from 50/5 to 0.1/5. As shown in Table 1 (Entry 5), the effect of using 10 equivs.
[Bmim]Cl was excellent. The yields and reaction time were monitored while the amount of [Bmim]Cl
was reduced successively to 0.02 equivs. A reduced molar quantity of [Bmim]Cl of 4 equivs. (Entry 8)
still resulted in successful dissolution of the starting material. The reaction effect was almost the same
as Entry 5. As the molar quantity of [Bmim]Cl was reduced to 2 equivs. (Entry 9), a small amount of
insoluble starting material was observed. Nevertheless, no obvious yield decline was measured. With

Molecules 2011, 16
4503
continuous reduction of the amount of [Bmim]Cl, the reaction time was prolonged, accompanied
by more amount of unreacted starting material. The explanation is that the amount of [Bmim]Cl
as catalyst in the system was relatively low, which consequently led to low reaction rates and
conversions. In addition, without enough [Bmim]Cl to dissolve the raw material in water, uneven
stirring in solid-liquid system resulted in low conversion. Therefore, the best molar ratio of [Bmim]Cl
to substrate was 4 to 1 (Entry 8).
2.3. Recycling of the [Bmim]Cl/water
The feasibility of recycling ionic liquids/H2O represents an important topic and performance
criterion of any industrial process. The proportion of [Bmim]Cl and water did not change much after
filtering off the products. This prompted us to investigate the recycling of the wet ionic liquid. After
isolated the product by filtration, the residual [Bmim]Cl/H2O of Table 1, Entry 8 was collected without
any treatment for the reuse. The reaction of acetoacetylaniline (1 equiv.), carbon disulfide (1.2 equivs.)
and 1,2-dibromoethane (1 equiv.) while reusing the wet ionic liquid was analyzed. The corresponding
α-oxoketene S,S-acetal was produced in a yield of 70% (Table 2, Entry 1). After filtering the product
by the same process as described above, the residual [Bmim]Cl/H2O was reused for a third, fourth and
fifth time. The results of subsequent studies (Table 2) indicated that the yield did not decline even in
the fifth run with reused [Bmim]Cl/water. This finding implied that wet ionic liquid can be recycled,
and the catalytic activity of [Bmim]Cl is not decreased.
Table 2. Recycling of [Bmim]Cl/water in synthesis of 7a.
Entry
Reuse
times
2
3
4
5
Reaction
medium
1a
CS2
BrCH2CH2Br Time a Yield b
(mmol) (mmol) (mmol)
(h)
5
6
6
7
(%)
70
65
65
66
1
2
3
[Bmim]Cl/H2O c
[Bmim]Cl/H2O d
[Bmim]Cl/H2O e
[Bmim]Cl/H2O f
5
5
5
5
6
6
6
6
5
5
5
5
4
a
b
The reaction time was recorded after the addition of 1,2-dibromoethane; Yields of 7a were
c
obtained by purification with column chromatography; [Bmim]Cl/H2O was obtained after
d
filtration the product of Table 1 Entry 8 and without any treatment; [Bmim]Cl/H2O was obtained
e
after filtration the product of Table 2 Entry 1 and without any treatment; [Bmim]Cl/H2O was
obtained after filtration the product of Table 2 Entry 2 and without any treatment; f [Bmim]Cl/H2O
was obtained after filtration the product of Table 2 Entry 3 and without any treatment.
2.4. The Synthesis of Different α-oxoketene S,S-acetals
To extend the applicability of this protocol, a series of substrates 1a-1e were subjected to the
reaction using the optimized conditions (Table 1, Entry 8). The results are summarized in Table 3.

Molecules 2011, 16
4504
Table 3. Preparation of α-oxoketene S,S-acetals 6a-9e from 1,3-dicarbonyl compounds 1
in [Bmim]Cl/H2O.
O
O
O
O
R
[Bmim]Cl / H2O / K2CO3
N
R
N
H
H
CS2
R1X (2--5)
S
S
R1 R1
1a--1e
6a--9e
b
Substrate
R
C6H5
C6H5
CH(CH2)5
CH(CH2)5
CH(CH2)5
o-Methylphenyl
o-Methylphenyl
-CH3
-CH3
-CH3
-(CH2)3CH3
-(CH2)3CH3
-(CH2)3CH3
Substrate
Time a
(h)
5
5
6
6
6
6
6
6
6
6
6
6
6
Yield
Entry
Product
1
2--5
X
Br
Br
Br
R1 R1
(%)
73
74
60
55
53
70
72
65
61
60
66
55
58
1
2
3
4
5
6
7
8
1a
1a
1b
1b
1b
1c
1c
1d
1d
1d
1e
1e
1e
2
3
3
4
5
2
3
3
4
5
3
4
5
-(CH2)3-
-(CH2)2-
-(CH2)2-
6a
7a
7b
8b
9b
6c
7c
7d
8d
9d
7e
8e
9e
Br -C2H5 -C2H5
I
-CH3
-CH3
Br
Br
Br
-(CH2)3-
-(CH2)2-
-(CH2)2-
9
Br -C2H5 -C2H5
10
11
12
13
I
-CH3
-CH3
Br
-(CH2)2-
Br -C2H5 -C2H5
-CH3 -CH3
I
a The reaction time was recorded after the addition of halohydrocarbon; b Yields of 6a-9e obtained
by purification with column chromatography.
The yields of cyclic α-oxoketene S,S-acetals (e.g., Entry 3) were higher than for acyclic α-oxoketene
S,S-acetals (Entries 4, 5). Series 1b, 1d and 1e also follow this regularity. It is possible that acyclic
α-oxoketene S,S-acetal molecules were less stable than cyclic ones. It is demonstrated from Table 3
that the reaction status of α-oxoketene S,S-acetals with naphthenic base, methyl and butyl was not as
efficient as of α-oxoketene S,S-acetals with phenyl groups. From Table 3, it was found that 1a and 1c
bear phenyls while the others do not, and the lone pair electrons on N can form p-π conjugation with
the phenyls which disperses the electronic density of the N atom. Without enough electron cloud, the
N atom was more resistant to nucleophilic attack by the carbonium ion of halohydrocarbon followed
by a Hofmann alkylation reaction mechanism [29,30]. The side reactions of 1a and 1c were reduced
while for 1b, 1d and 1e no phenyl p-π conjugation is possible. Using the optimized experimental
procedures the results also revealed that the series 1b, 1d and 1e were too sensitive to variations. The
reaction always led to poor results, even if the temperature was slightly higher. Therefore, different
structural skeletons have different effects on this reaction. Further investigations are necessary to
analyze this in more detail.
On the basis of these results, in combination with a former study [8], a tentative mechanism of
[Bmim]Cl catalytic synthesis of α-oxoketene S,S-acetals was shown in Scheme 1. Enolates 10 and 11
can be derived from deprotonation of 1,3-dicarbonyl compounds in the present of [Bmim]Cl/H2O by a
weak base. Then enolates reaction with CS2 resulted in 12 and 12 isomerized to give the unsaturated

Molecules 2011, 16
4505
monothiolate anion 13. Compound 13 undergoes the S-alkylation with the halohydrocarbon to yield
the product α-oxoketene S,S-acetal.
Scheme 1. A tentative mechanism of [Bmim]Cl catalytic synthesis of α-oxoketene S,S-acetals.
O
O
O
O
C4H9
R
N
N CH3
O
O
C4H9
N
N CH3
K2CO3/H2O
[Bmim]Cl
R
N
R
N
N
H
H
H
1
10
11
O
O
S
O
O
O
O
R
R
N
2 R1X/[Bmim]Cl
K2CO3/H2O
N
H
CS2, r.t.
R
H
N
S
N
H
HS
S
C4H9
N
N CH3
R1S SR1
C4H9
N CH3
12
13
3. Experimental
3.1. Preparation of Materials
All reagents used were purchased from the Lanzhou Institute of Chemical Physics, China National
Medicines Corporation Ltd and other commercial suppliers and were used as supplied unless otherwise
stated. TLC was carried out on a Merck Kieselgel GF254. Purification or separation of product was
carried out with flash column chromatography using 300–400 mesh silica gel. 1H-NMR and 13C-NMR
spectra were determined using TMS as an internal reference with a Bruker Avance-300 NMR
spectrometer operating at 300 MHz and 75 MHz, respectively. MS analysis was carried out on an
API-3000 LC-MS-MS instrument.
N-Cyclohexylacetoacetamide/N-Butyl-3-oxo-butanamide was synthesized according to the previous
literature method [31]. Diketene (10 mmol) was added dropwise in a mixture of cyclohexylamine/
1-butylamine (10 mmol) and benzene or water (20 mL) over 1 hour at 0 °C. Then the resulting mixture
was stirred for 2 h at room temperature. After the reaction completed as indicated by TLC, extraction
of the resulting mixture and purification the crude product furnished N-cyclohexylacetoacetamide/N-
butyl-3-oxo-butanamide in 94%/89% yield.
3.2. General Procedure for the Preparation of α-oxoketene S,S-acetals 6a-7a, 7b-9b and 6c-7c
1,3-Dicarbonyl compounds (5 mmol) and [Bmim]Cl (20 mmol) were added to water (15 mL) at
0 °C. After stirred for 3 min, potassium carbonate (12.5 mmol) was added and then the mixture
was stirred for an hour at 0 °C. Then carbon disulfide (6 mmol) was added, and the mixture was stirred
for another hour and then halohydrocarbon [5 mmol, 1,3-dibromopropane (6a and 6c), 5 mmol
1,2-dibromoethane (7a, 7b and 7c), 10 mmol bromoethane (8b) or 10 mmol iodomethane (9b)] was
added dropwise over 30 min, then the resulting mixture was stirred for about 5-6 hours at room

Molecules 2011, 16
4506
temperature. Because the product was not dissolved in the [Bmim]Cl/H2O system and acted as solid
state, the product was filtrated and washed with water and the residual liquid could be reused without
any treatment. After drying under vacuum for 5 hours, a crude solid was obtained. Purification by
column chromatography afforded the product as a yellowish or white solid in moderate yield. All
1
compounds exhibited spectral data consistent with their structures. H-NMR, 13C-NMR and MS
spectral data of compounds were shown as below:
1
N-Phenyl-2-(1,3-dithian-2-ylidene)-3-oxobutanamide (6a): white solid, H-NMR (CDCl3) δ: 8.14 (s,
1H, -NH-), 7.65(d, J = 7.9 Hz, 2H, H-Ph), 7.37 (t, J = 7.9 Hz, 2H, H-Ph), 7.16 (t, J = 7.4 Hz, 1H,
13
H-Ph), 2.98 (t, J = 7.0 Hz, 4H, -CH2-), 2.39 (s, 3H, -CH3), 2.32–2.16 (m, 2H, -CH2-); C-NMR
(CDCl3) δ: 193.88, 164.78, 164.27, 137.86, 132.42, 129.12, 124.71, 119.99, 29.35, 29.17, 28.94, 23.98.
MS (ESI): [M+H]+ 294.1.
N-Phenyl-2-(1,3-dithiolan-2-ylidene)-3-oxobutanamide (7a): white solid, 1H-NMR (CDCl3) δ: 8.19 (s,
1H, -NH-), 7.65 (d, J = 7.4 Hz, 2H, H-Ph), 7.38 (t, J = 7.9 Hz, 2H, H-Ph), 7.17 (t, J = 7.4 Hz, 1H,
H-Ph), 3.48–3.41 (m, 2H, -CH2-), 3.40–3.32 (m, 2H, -CH2-), 2.42 (s, 3H, -CH3); 13C-NMR (CDCl3) δ:
192.91, 170.10, 165.19, 137.68, 129.16, 124.82, 123.77, 120.09, 38.54, 36.62, 28.63. MS (ESI):
[M+H]+ 280.0.
1
N-Cyclohexyl-2-(1,3-dithiolan-2-ylidene)-3-oxobutanamide (7b): white solid, H-NMR (CDCl3) δ:
5.84 (d, J = 7.8 Hz, 1H, -NH-), 4.04–3.82 (m, 1H, -CH-), 3.47–3.34 (m, 2H, -CH2-), 3.34–3.21 (m, 2H,
-CH2-), 2.28 (s, 3H, -CH3), 2.09–1.93 (m, 2H, -CH2-), 1.82–1.67 (m, 2H, -CH2-), 1.65–1.09 (m, 6H,
13
-CH2-CH2-CH2-); C-NMR (CDCl3) δ: 191.76, 167.13, 166.58, 124.19, 48.78, 38.68, 36.29, 32.82,
27.86, 25.53, 24.78. MS (ESI): [M+H]+ 286.1.
N-Cyclohexyl-2-(bis(ethylthio)methylene)-3-oxobutanamide (8b): white solid, 1H-NMR (CDCl3) δ: 6.05
(d, J = 7.1 Hz, 1H, -NH-), 3.91–3.77 (m, 1H, -CH-), 2.88 (q, J = 7.4 Hz, 4H, -S-CH2-), 2.39 (s, 3H,
-CO-CH3), 2.07–1.85 (m, 2H, -CH2-), 1.70–0.98 (m, 8H, -CH2-CH2-CH2-CH2-), 1.27 (t, J = 7.4 Hz,
13
6H, -CH3); C-NMR (CDCl3) δ: 197.76, 164.04, 147.26, 142.22, 48.61, 32.78, 30.13, 29.29, 25.53,
24.73, 14.76. MS (ESI): [M+H]+ 316.1.
1
N-Cyclohexyl-2-(bis(methylthio)methylene)-3-oxobutanamide (9b): white solid, H-NMR (CDCl3) δ:
5.99 (d, J = 7.2 Hz, 1H, -NH-), 3.93–3.76 (m, 1H, -CH-), 2.41 (s, 6H, -S-CH3), 2.37 (s, 3H, -CH3), 1.95
(dd, J = 12.8, 3.3 Hz, 2H, -CH2-), 1.78–1.51 (m, 4H, -CH2-CH2-), 1.47–1.02 (m, 6H, -CH2-CH2-CH2-);
13C-NMR (CDCl3) δ: 196.94, 164.33, 152.86, 139.40, 48.67, 32.77, 29.79, 25.53, 24.74, 18.81, 17.81.
MS (ESI): [M+H]+ 288.1.
N-(2-Methylphenyl)-2-(1,3-dithian-2-ylidene)-3-oxobutanamide (6c): white solid, 1H-NMR (CDCl3) δ:
8.00 (d, J = 8.3 Hz, 1H, H-Ph), 7.88 (s, 1H, -NH-), 7.26–7.17 (m, 2H, H-Ph), 7.10 (t, J = 7.5 Hz, 1H,
H-Ph), 3.00 (t, J = 6.9 Hz, 4H, -CH2-), 2.44 (s, 3H, -CO-CH3), 2.32 (s, 3H, CH3-Ph), 2.31–2.21 (m, 2H,
-CH2-); 13C-NMR (CDCl3) δ: 194.75, 164.54, 163.96, 135.55, 132.28, 130.57, 128.92, 126.84, 125.33,
122.61, 29.41, 28.98, 24.08, 18.00. MS (ESI): [M+H]+ 308.1.

Molecules 2011, 16
4507
1
N-(2-Methylphenyl)-2-(1,3-dithiolan-2-ylidene)-3-oxobutanamide (7c): white solid, H-NMR (CDCl3)
δ: 8.08 (s, 1H, H-Ph), 7.96 (d, J = 6.5 Hz, 1H, -NH-), 7.26–7.20 (m, 2H, H-Ph), 7.15–7.04 (m, 1H,
H-Ph), 3.52–3.42 (m, 2H, -CH2-), 3.41–3.32 (m, 2H, -CH2-), 2.47 (s, 3H, -CO-CH3), 2.34 (s, 3H,
CH3-Ph); 13C-NMR (CDCl3) δ: 193.33, 170.13, 165.16, 135.55, 130.64, 129.36, 126.84, 125.46,
123.68, 122.87, 38.45, 36.71, 28.87, 18.11. MS (ESI): [M+H]+ 294.1.
3.3. General Procedure for the Preparation of α-oxoketene S,S-acetals 7d-9d and 7e-9e
1,3-Dicarbonyl compounds (5 mmol) and [Bmim]Cl (20 mmol) were added into water (15 mL) at
0 °C. After stirring for 3 min, potassium carbonate (12.5 mmol) was added and then the mixture was
stirred for another hour at 0 °C. Then carbon disulfide (6 mmol) was added, and the mixture was
stirred for another hour and then halohydrocarbon [5 mmol, 1,2-dibromoethane (7d and 7e), 10 mmol
bromoethane (8d and 8e) or 10 mmol iodomethane (9d and 9e)] was added dropwise over 30 min, then
the resulting mixture was stirred for about 6 hours at room temperature. Because the product was
dissolved in the [Bmim]Cl/H2O system and acted as liquid state, the product was extracted by ether for
four times and the residual liquid could be reused without any treatment. Purification with column
chromatography afforded the product as a yellowish solid or yellow oil in moderate yield.
1
N-Methyl-2-(1,3-dithiolan-2-ylidene)-3-oxobutanamide (7d): yellowish solid, H-NMR (CDCl3) δ:
6.14 (s, 1H, -NH-), 3.47–3.26 (m, 4H, -CH2-), 2.97 (d, J = 4.9 Hz, 3H, CH3-N), 2.32 (s, 3H, -CH3);
13C-NMR (CDCl3) δ: 192.22, 168.17, 123.73, 38.62, 36.35, 28.15, 26.71. MS (ESI): [M+H]+ 218.0.
1
N-Methyl-2-(bis(ethylthio)methylene)-3-oxobutanamide (8d): yellow solid, H-NMR (CDCl3) δ: 6.31
(s, 1H, -NH-), 2.90 (q, J = 7.4 Hz, 4H, -CH2-), 2.89 (d, J = 4.9 Hz, 3H, CH3-N), 2.43 (s, 3H, -CO-CH3),
1.29 (t, J = 7.4 Hz, 6H, -CH3); 13C-NMR (CDCl3) δ: 198.52, 165.28, 147.45, 141.76, 30.40, 29.21,
26.56, 14.69. MS (ESI): [M+H]+ 248.1.
N-Methyl-2-(bis(methylthio)methylene)-3-oxobutanamide ( ): yellow solid, 1H NMR (CDCl ) δ: 6.25
9d
-
3
(s, 1H, -NH-), 2.88 (d, J = 4.9 Hz, 3H, N-CH3), 2.40 (s, 3H, -S-CH3), 2.40(s, 3H, -S-CH3), 2.39 (s, 3H,
-CO-CH3); 13C-NMR (CDCl3) δ: 197.78, 165.54, 152.96, 138.93, 30.07, 26.62, 18.17. MS (ESI):
[M+H]+ 220.0.
1
N-(n-Butyl)-2-(1,3-dithiolan-2-ylidene)-3-oxobutanamide (7e): yellowish solid, H-NMR (CDCl3) δ:
6.09 (s, 1H, -NH-), 3.48–3.23 (m, 6H, -CH2-), 2.28 (s, 3H, -CO-CH3), 1.65–1.52 (m, 2H, -CH2-),
13
1.49–1.29 (m, 2H, -CH2-), 0.93 (t, J = 7.3 Hz, 3H, -CH3); C-NMR (CDCl3) δ: 192.00, 167.61,
167.50, 124.01, 39.80, 38.65, 36.33, 31.44, 28.01, 20.23, 13.75. MS (ESI): [M+H]+ 260.1.
N-(n-Butyl)-2-(bis(ethylthio)methylene)-3-oxobutanamide (8e): yellow oil, 1H-NMR (CDCl3) δ: 6.24
(s, 1H, -NH-), 2.07 (q, J = 5.9 Hz, 2H, N-CH2-), 2.95–2.80 (m, 4H, -S-CH2-), 2.40 (s, 3H, -CO-CH3),
1.53–1.45 (m, 2H, -CH2-), 1.38–1.31 (m, 2H, -CH2-), 1.30–1.21 (m, 6H, -CH2-), 0.91 (t, J = 6.9 Hz,
3H, -CH3); 13C-NMR (CDCl3) δ: 198.30, 164.67, 147.07, 142.12, 39.63, 31.37, 30.31, 29.19, 20.15,
14.72, 13.71. MS (ESI): [M+H]+ 290.1.

Molecules 2011, 16
4508
N-(n-Butyl)-2-(bis(methylthio)methylene)-3-oxobutanamide ( ): yellow oil, 1H NMR (CDCl ) δ: 6.22
9e
-
3
(s, 1H, -NH-), 3.34–3.30 (m, 2H, N-CH2-), 2.40–2.36 (m, 9H, -CO-CH3, -S-CH3), 1.53–1.48 (m, 2H,
-CH2-), 1.37–1.32 (m, 2H, -CH2-), 0.94–0.87 (m, 3H, -CH3); 13C-NMR (CDCl3) δ: 197.44, 165.02,
152.80, 139.23, 39.69, 31.32, 29.95, 20.15, 18.19, 13.72. MS (ESI): [M+H]+ 262.1.
4. Conclusions
In conclusion, a clean, environmentally friendly method has been developed for the synthesis of
α-oxoketene S,S-acetals in moderate yields based on the reaction of 1,3-dicarbonyl compounds with
carbon disulfide and halohydrocarbon in the presence of potassium carbonate in a [Bmim]Cl/water
homogeneous system. A simple procedure, mild conditions, moderate yields, multiple recycling of wet
ionic liquid and environmental tolerability make the present protocol highly attractive for academic
research and practical applications.
Acknowledgments
We gratefully acknowledge the financial supports by Key Program for Science and Technology
Development of Harbin (2009AA3BS083), Heilongjiang Province Science Foundation for Excellent
Youths (JC200704), Agricultural Science and Technology Achievements Transformation Fund
Program (2009GB23600514), Project for Distinguished Teacher Abroad, Chinese Ministry of
Education (MS2010DBLY031), Fundamental Research Funds for the Central Universities
(DL09EA04), the Special Fund of Forestry Industrial Research for Public Welfare of China
(201004040) and Prof. Qun Liu for the guidance.
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