4034
S. Sathishkumar et al. / Tetrahedron Letters 56 (2015) 4031–4035
Aldrich, Spectrochem, Alfa Aesar, TCI Chemicals, Qualigens,
Lancaster and used without further purification. The compound
3b, 3c, 3e, 6b, 8b were prepared by following the reported
procedures.9
(hexane/EtOAc) to afford the iodo compound 5a, as pale yellow col-
our oily liquid.
General procedure for the synthesis of allylide 9 (9a as an
example)
The 1H & 13C spectra for compounds 4, 5(a–c), 7a, 9(a–b), 11b,
12b were run in deuterated chloroform. For compound 9c, they
were run in deuterated dimethyl sulfoxide using 300 MHz &
75 MHz respectively on Bruker 300 MHz Avance NMR spectrome-
ter. The 1H and 13C spectra for compounds 11a, 12a were taken
in deuterated chloroform using Bruker 400 MHz Avance NMR spec-
trometer. Chemical shifts (d) are reported as parts per million
(ppm) with reference to tetramethylsilane (TMS) (dH = 0.00 ppm)
unless otherwise stated. The coupling constants (J) are reported
in Hz and signal multiplicities are reported as singlet (s), doublet
(d), triplet (t), quartet (t), doublet of doublet (dd), multiplet (m).
Melting points are uncorrected and were recorded on Veego
Model VMP-PM melting point apparatus. IR spectra were recorded
on Perkin Elmer FT-IR. Mass spectroscopy was recorded on
Shimadzu QP2010 MS detector using EI technique. High-resolution
mass spectra (HRMS) were recorded on a Micromass EI mass spec-
trometer. Single crystal XRD of compound 4 was taken in Bruker
AXS Kappa APEXII CCD Diffractometer.
Sodium hydride (60%), (1.88 g, 0.047 mol), washed twice with
hexane to remove the paraffin oil, was added to a clean well dried
RB flask. Traces of solvent were removed by applying nitrogen
using evacuated carousel or ampoules. To the dried sodium
hydride, dry DMF (30 mL) was added under nitrogen atmosphere,
followed by trimethylsulfoxonium iodide (10.35 g, 0.047 mol) in
single lot and the contents were stirred for 60 min at 40–45 °C.
This solution was added to a mixture of the compound 3a (10 g,
0.046 mol) in DMF (5 mL) at 0 °C under nitrogen atmosphere over
a period of 15 min. The completion of reaction was checked by TLC.
Then the reaction mixture was maintained for a period of 1–2 h at
room temperature and quenched by adding the reaction mixture
into ice cold water. The aqueous mixture was extracted with chlo-
roform and the organic layer was washed with brine solution. The
organic layer was concentrated and purified using column chro-
matography on silica gel (hexane/EtOAc) to afford the allylide 9a
as colourless solid (mp 123 °C).
Procedure for the synthesis of 4-ethoxycarbonyl-3-hydroxy-2-
methyl-thiabenzene-1-oxdie 4
General procedure for the synthesis of dialkyl 2-(2-chloro-
ethylidene)malonate 11 (11a as an example)
Sodium hydride (60%), (1.88 g, 0.047 mol), washed twice with
hexane to remove the paraffin oil, was added to a clean well dried
RB flask. Traces of solvent were removed by applying nitrogen using
evacuated carousel or ampoules. To the dried sodium hydride, dry
DMF (20 mL) was added under nitrogen atmosphere, followed by
trimethylsulfoxonium iodide, (2.07 g, 0.0094 mol) in single lot.
The contents were stirred for 60 min at 40–45 °C. The ylide solution
was cooled to 0 °C under nitrogen atmosphere. A solution of 3a
(1.0 g, 0.0046 mol) in DMF (5 mL) was added into the ylide solution
in single lot at 0 °C. The reaction mixture was maintained at 0 °C for
a period of 2 h and quenched with water at 5 °C. The aqueous mix-
ture was extracted with chloroform and the organic layer was
washed with brine solution. The organic layer was concentrated
and the crude product purified using column chromatography on
silica gel (hexane/EtOAc) to afford 4 as pale yellow colour solid.
(mp 112 °C, kmax = 273 nm). (Lit.7a mp 111–112 °C).
The allylide 9a, (3.00 g, 0.012 mol) was taken in THF (10 mL),
treated with anhydrous Lithium chloride, (0.51 g, 0.012 mol) and
methanesulfonic acid, (1.15 g, 0.012 mol). The reaction mixture
was refluxed for 4–5 h. The completion of reaction was checked by
TLC. The reaction mixture was quenched by adding the mixture into
ice cold water. The aqueous mixture was extracted with Diethyl
ether and the organic layer was washed with brine solution. The
organic layer was concentrated and purified using column chro-
matography on silica gel (hexane/EtOAc) to afford the dialkyl 2-(2-
chloroethylidene)malonate 11a as pale yellow colour oily liquid.
General procedure for the synthesis of dialkyl 2-(2-bromo-
ethylide-ne)malonate 12 (12a as an example)
The allylide 9a, (3.00 g, 0.012 mol) was taken in dichloro-
methane (10 mL) and treated with aqueous hydrobromic acid,
(2.06 g, 0.012 mol) at 0 °C. The reaction mixture was stirred for
about 30–45 min at 0 °C. The completion of reaction was checked
by TLC. The reaction mixture was quenched with ice cold water.
The organic layer was washed with brine solution, concentrated
and purified using column chromatography on silica gel
(hexane/EtOAc) to afford the dialkyl 2-(2-bromoethylidene)- mal-
onate 12a as pale yellow colour oily liquid.
General procedure for the synthesis of (2-iodoethylidene)-
malonates and cyanoacetates 5 and 7 (5a as an example)
Sodium hydride (60%), (1.88 g, 0.047 mol), washed twice with
hexane to remove the paraffin oil, was added to a clean well dried
RB flask. Traces of solvent were removed by applying nitrogen
using evacuated carousel or ampoules. To the dried sodium
hydride, dry DMF (30 mL) was added under nitrogen atmosphere,
followed by trimethylsulfoxonium iodide (10.35 g, 0.047 mol) in
single lot and the contents were stirred for 60 min at 40–45 °C.
This solution was added to a mixture of the compound 3a (10 g,
0.046 mol) in DMF (5 mL) at 0 °C under nitrogen atmosphere over
a period of 15 min. The completion of reaction was checked by TLC.
Then the reaction mixture was maintained for a period of 1–2 h at
room temperature and quenched by adding the reaction mixture
into a solution of aqueous hydroiodic acid (10%) solution at 0 °C.
The aqueous mixture was extracted with chloroform and the
organic layer was washed with 10% sodium thiosulfate solution
to remove the excess iodine. The organic layer was concentrated
and purified using column chromatography on silica gel
Acknowledgments
We gratefully acknowledge the facility support from Shasun
Pharmaceuticals Ltd Chennai, India and Nuray Chemicals Pvt. Ltd,
Chennai, India. Department of Science and Technology, Govt. of
India for funding and SAIF—IIT Madras, India., for analytical
support.
Supplementary data
Supplementary data associated with this article can be found, in
Sathishkumar
