Application of commercially available anhydrous potassium fluoride for a convenient synthesis of ketene dithioacetals

Article abstract of DOI:10.1039/a901038f

Commercially available anhydrous KF without activation or solid support promotes condensation between active methylene compounds, carbon disulfide and an alkylating agent in dry DMF to allow the preparation of a variety of ketene dithioacetals in fair to good yields under ambient conditions.

Full text of DOI:10.1039/a901038f

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492 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 492^493y
Application of Commercially Available
Anhydrous Potassium Fluoride for a Convenient
Synthesis of Ketene Dithioacetalsy
Sabir H. Mashraqui* and Harini Hariharasubrahmanian
Department of Chemistry, University of Mumbai, Vidyanagari, Santacruz (E), Mumbai 400 098,
India
Commercially available anhydrous KF without activation or solid support promotes condensation between active
methylene compounds, carbon disulfide and an alkylating agent in dry DMF to allow the preparation of a variety
of ketene dithioacetals in fair to good yields under ambient conditions.
Ketene dithioacetals are versatile synthons in the area of
C^C bond formation, functional group manipulations
and in the synthesis of carbo- and heterocyclic systems.1
A general procedure for preparing ketene dithioacetals is
based on the condensation of carbanions with CS2, followed
by in situ bis-thioalkylations of the resultant ketene
dithiolate anions. These condensations have been described
using a variety of basic reagents, which include potassium
hydroxide, sodium hydride, potassium tert-butoxide,
sodium tert-amylate, n-butylithium, lithium diisopropyl-
amide (LDA), lithium dicyclohexylamide and lithium
period of up to 20 h after the addition of ca. 2.5 equiv.
of methyl iodide. Of the various solvents examined, we
found anhydrous DMF to be a solvent of choice in terms
of high e¤ciency and yield (2 h for complete conversion,
77% isolated yield of 7). In contrast, the same reaction
in 1,4-dioxane, THF or CH3CN showed relatively
poor conversions (12^30%) even after 20 h under ambient
conditions.
To demonstrate the generality of our procedure, the syn-
thesis of a number of ketene dithioacetals was attempted
with KF/DMF. Our results, collected in the Table 1, clearly
show that a variety of active methylene compounds, such
hexamethyldisilazide.2
In addition, Lawesson and
coworkers3 have reported the synthesis of ketene
dithioacetals of some active methylene compounds under
phase transfer catalysis. However, lack of su¤cient
generality, variable yields and instabilities of ketene
dithioacetals under strong basic conditions are limitations
of many of these procedures.
Table 1 Preparation of ketene dithioacetals using anhydrous
KF/DMF systema
Active
Entry methylene
compound
Yieldc Mp
(%)
Alkylating
Time
(t /h)
Productb
Ph Ph
In recent years, ionic £uoride salts, either alone or in the
form of coated reagents or in combination with complexing
agents such as crown ethers, have found increasing
applications in organic synthesis through the intermediacy
of carbanions and heteroatom nucleophiles.4;5 Being mild
and non-nucleophilic in nature, the £uoride ion method-
ology appeared to us of interest for preparing ketene
dithioacetals. Indeed, Villemin and Abdelkrim6 have
reported the application of activated anhydrous KF
supported on alumina for the synthesis of ketene
dithioacetals. Curiously, these authors either failed to study
or report if KF directly, without activation or solid support,
could be used to promote these reactions. During the course
of our work, we have been able to de¢ne conditions that
allow, without prior activation or solid support, the direct
use of commercial anhydrous KF for preparing ketene
dithioacetals as shown in the generalized reaction (1).
agent (RX)
(T / ˚C)
62–64(66)6
76–78
Ph Ph
1
7
8
9
77
71
60
CH3I
C2H5I
PhCH2Cl
CH2=CHCH2Cl 3
2
4
3
2
3
4
O
O
O
O
R
142–144
1
R
70–72(74)3
10 40
S
S
Ph Ph
CH3 CH3
65 57–59(60)6
57 106–108
11
12
5
6
CH3I
PhCH2Cl
2
3
O
R
O
R
O
O
2
S
S
CH3 CH3
O
O
BrCH2CH2Brd
135–38(138)6
50
13
7
4
S
S
NC
CN
14 43 73–75(76)7
R
15 25 oil
NC
CN
8
9
CH3I
PhCH2Cl
4
6
R
3
S
S
O
10
PhCH2Cl
6
4
16 40 88–89(87)8
O
X
X
X
X
SR
SR
CS2, RX
O
O
(1)
4
5
Ph
S
S
Ph
KF / DMF
H5C2O
O
OC2H5
36 oil6
O
H5C2O
OC2H5
X = electron-withdrawing group
11
PhCH2Cl
O
O
Ph
S
S
Ph
17
As
dibenzoylmethane 1 into the corresponding dimethylketene
dithioacetal (Table 1) in di¡erent solvents such as
1,4-dioxane, THF, CH3CN and DMF at room temperature.
The reaction mixture, which consisted of 10 mmol of 1,
excess of CS2 and 20 molar equivalents of commercial grade
anhydrous KF, was initially stirred in the aforementioned
solvents for 10 min at room temperature and for a further
a
test case, we studied the conversion of
O
O
O
124–126(126)7
52
3
6
8
12
13
14
CH3I
CH3CH2CH2Br
PhCH2Cl
SR
SR
7
79
94–96
60
126–128
18
19
20
O
6
aExcept where mentioned otherwise, all reactions conducted at
room temperature (2^8 h) using 10mmol of active methylene
compound and 10^12 mmol of alkylating agent as described in the
general procedure. bAll known products were fully characterized
by physical and spectral data which agree with the literature
values. cYields refer to pure products. d5 mmol of dibromoethane
used.
* To receive any correspondence (e-mail: shm@chbu.ernet.in).
y 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).

View Article Online
J. CHEM. RESEARCH (S), 1999 493
Table 2 Analytical and spectral data for the new ketene dithioacetals
Found(required)(%)
1
Compound Formula
C
H
N
S
nmax=cm
dH(CDCl3)
8
C
20H20O2S2
67.21
(67.38) (5.65)
5.89
^
^
18.22
(17.99)
1720, 1680, 1560
1.1 (6H, t, CH3CH2^),
2.7 (4H, q, CH3CH2^),
7.2^8.1 (10 H, m, arom.)
3.9 (4 H, s, SCH2),
7.0^8.05 (20 H, m, arom.)
2.1 (6 H, s, SCH3),
9
C
30H24O2S2
18H20O2S2
74.78
(74.97) (5.03)
65.39 5.89
(65.03) (6.06)
5.29
^
^
^
^
13.62
(13.34)
19.02
1660, 1640, 1600
1720, 1682, 1663
12
C
(19.29)
4.1 (4 H, s, PhCH2^),
7.2 (10 H, m, arom.)
15a
19
C18H14N2S2
66.77
(67.05) (4.38)
62.71 6.13
(62.73) (5.93)
4.65
8.60
(8.69) (19.89)
^
^
19.62
1580, 1504, 1083
1678, 1621, 1606
4.45 and 4.50 (2 H, s, each, ^SCH2^),
7.44 and 7.5 (5 H, s, each H arom.)
1.0 (6 H, t, CH3CH2^),
1.7 (4 H, t, ^SCH2CH2^),
3.1 (4 H, t, ^SCH2CH2^),
7.6 (H, m, H arom.)
C16H18O2S2
20.66
(20.89)
20
C24H18O2S2
71.39
(71.61) (4.51)
4.28
^
^
16.22
(15.93)
1703, 1677, 1600
4.3 (4 H, s, SCH2^),
7.2 (10 H, s, H arom.),
7.7^7.9 (4 H, m, H arom.)
aIR band for the CN group either absent or too weak to be detected.
extracted with ethyl acetate (3 Â 25 ml) and the extract washed several
as dibenzoyl methane, acetyl acetone, dimedone, 1,3-
indanedione, diethyl malonate and malononitrile, success-
fully participate in the reaction, giving fair to good yields
of ketene dithioacetals. The structural characterization
for unknown ketene dithioacetals is based on elemental
analysis and spectral data (Table 2). However, attempts
to e¡ect the synthesis of ketene dithioacetals derived from
simple aliphatic or aromatic ketones were unsuccessful2;6
presumably because of the failure of these ketones to
undergo deprotonation under the present conditions.
The sharp signals and the simplicity of the 1H NMR
spectra (Table 2) suggest the presence of either a single
predominant conformation or fast equilibria involving dif-
ferent conformers for these ketene dithioacetals. The other-
wise symmetrical oxo-ketene dithioacetals (Table 2;
compounds 8, 9, 12, 19 and 20) were all found to display
split absorption bands for the carbonyl groups in their
IR spectra. Such splittings, which ¢nd ample precedence
in the literature,9 may be attributed to the vibrational
coupling of carbonyl functions with either the fundamental
vibration of the p-bond or Fermi resonance.10
times with water. Finally, the extract was dried over anhydrous
Na2SO4 and concentrated to give
a yellow solid which upon
crystallization from ethanol provided 2.5 g (77% yield ) of ketene
dithioacetal 7, mp 62^64 8C (lit.6 mp 66 8C).
We thank CSIR, New Delhi for generous ¢nancial
support.
Received, 8th February 1999; Accepted, 22nd April 1999
Paper E/9/01038F
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In summary, we have described a procedure for the direct
application of commercially available anhydrous KF,
without the need of activation or solid support, for the
preparation of a variety of ketene dithioacetals of active
methylene compounds in fair to good yields in what appears
to be a simpler and more convenient alternative to other
available methods.2;3;6
4
5
Experimental
Melting points (uncorrected) were determined on a Gallenkamp
melting point apparatus. IR spectra were recorded on a Shimadzu
FTIR-4200 spectrophotometer either as oil ¢lms or KBr discs.
1H NMR spectra were recorded on a Varian EM-360L (60 MHz)
spectrometer with TMS as internal standard.
General Procedure for the Preparation of Ketene Dithioacetals.ö
To a vigorously stirred solution of dibenzoyl methane (1) (2.24 g,
10 mmol) in dry DMF (20 ml) were added, at room temperature, com-
mercial grade dry KF (12 g), freshly distilled CS2 (0.8 ml, 12 mmol)
and methyl iodide (1.3 ml, 20 mmol). The initial yellow reaction
mixture, which rapidly turned red in colour, was stirred for a period
of 2 h. At this point the reaction mixture was diluted with water,
6
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8
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9
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