An expeditious one-pot synthesis of thiiranes from α-halo ketones in solvent-free conditions using microwaves

Article abstract of DOI:10.1055/s-2002-35222

Thiiranes are obtained in excellent yields and with high diastereoselectivity upon microwave irradiation of a mixture of α-haloketones, O,O-diethyl hydrogen phosphorodithioate and alumina-supported sodium borohydride in solvent-free conditions.

Full text of DOI:10.1055/s-2002-35222

2344
SHORT PAPER
An Expeditious One-Pot Synthesis of Thiiranes from -Halo Ketones in
Solvent-Free Conditions Using Microwaves
O
ne-Pot Synthe
a
sis of
T
hiir
l
anes from -H
D
alo Ketones har S. Yadav,* Ritu Kapoor
Department of Chemistry, University of Allahabad, Allahabad 211 002, India
Fax +91(532)545021; E-mail: lds-yadav@hclinfinet.com
Received 19 July 2002; revised 21 August 2002
based leaving groups,11 we have devised a microwave
Abstract: Thiiranes are obtained in excellent yields and with high
diastereoselectivity upon microwave irradiation of a mixture of
haloketones, O,O-diethyl hydrogen phosphorodithioate and alumi-
(MW)-expedited, one-pot procedure for an efficient syn-
thesis of thiiranes 3 from -halo ketones 1 using O,O-di-
ethyl hydrogen phosphorodithioate 2 and alumina-
supported sodium borohydride (Scheme 1). The forma-
tion of thiiranes was highly diastereoselective. The dia-
-
na-supported sodium borohydride in solvent-free conditions.
Key words: -haloketones, thiiranes, stereoselective synthesis, mi-
crowaves, solvent free, alumina supported
1
stereomer ratios of crude products were checked by H
NMR, prior to purification, to ensure correct and true dia-
stereomer ratios are reported.
Thiiranes are the simplest sulfur heterocycles and occur in
nature.1 These have been used advantageously in the phar-
maceutical, polymer, pesticide and herbicide industries.2
Recently, the utility of thiirane intermediates has been
demonstrated in a synthesis of thioglycosides.3 Most of
the synthetic methods available for the synthesis of thi-
iranes suffer from disadvantages such as poor yields,4 ex-
tended reaction times,5 formation of several by-products,5
and use of moisture sensitive,6 and foul smelling7 reagents
which must be handled with care.
The envisaged synthesis of 3 from 1 in its entirety in-
volves a simple mixing of an -halo ketone 1, O,O-dieth-
yl hydrogen phosphorodithioate 2 and alumina-supported
sodium borohydride followed by irradiating the mixture
in an unmodified domestic microwave oven for the time
specified in Table 1. The extraction of the product into
dichloromethane affords thiiranes 3 in excellent yields
(81–94%) and diastereoselectivity (89–100%) (Table 1).
For comparison purposes, the temperature of the bulk re-
action mixture was also measured immediately after irra-
diation. That the effect of microwaves may not be purely
thermal9,12 is supported by the fact that the reaction did not
even go to 50% completion after 15 hours at the same tem-
perature when conventional heating using an oil bath was
employed (Table 1).
Organic synthesis under microwave (MW) irradiation has
attracted much attention owing to several advantages,
such as rapid reaction rates and higher yield of pure prod-
ucts,8,9 as a consequence of the selective absorption of mi-
crowave energy by polar molecules or polar transition
state intermediates formed during the course of the reac-
tion.9 In the recent past, the emphasis has shifted in favor
of the use of MW-methodology under solvent-free
conditions8 because solvents are often expensive, hazard-
ous, difficult to remove in case of solvents with high boil-
ing points, and are agents that pollute the environment.
Further, this approach provides an opportunity to work
with open vessels, which avoids the risk of the build up of
high pressures, and enhances the possibility of scaling up
the reactions on a preparative scale. Recently, microwave-
assisted reduction of carbonyl compounds in the solid
state using NaBH4-Al2O3 has been reported.10
The formation of thiiranes 3 is best explained by reductive
cyclization of 5 involving the intramolecular attack of the
alkoxide ion 6 on the phosphorus atom as depicted in
Scheme 2. This assumption is supported by the isolation
of the parent alcohol of the alkoxide ion 6 during the
course of the reaction and its exclusive conversion into the
corresponding thiiranes 3 on treatment with a base, such
as sodium hydride in t-buatanol, which facilitates the
alkoxide ion formation.
When -bromo ketones were used, the yield of 3 was mar-
ginally higher than that with -chloro ketones (Table 1,
entries 2, 3, 6, 7, 8, 9). Similarly, the halo ketones in
which the halogen is attached to the primary carbon fur-
Inspired by the above reports and in pursuing our work on
new synthetic routes involving sulfur- and phosphorus-
Scheme 1
Synthesis 2002, No. 16, Print: 14 11 2002.
Art Id.1437-210X,E;2002,0,16,2344,2346,ftx,en;Z10402SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

SHORT PAPER
One-Pot Synthesis of Thiiranes from -Halo Ketones
2345
Scheme 2
nished better yields than that bearing the halogen at the afforded invariably higher yields (Table 1, entries
secondary carbon (Table, entries 1, 2, 4, 5, 8). However, 6, 7, 10, 11).
the halo ketones having the halogen at the benzylic carbon
In summary, we have developed a general method for an
expeditious, one-pot synthesis of thiiranes from readily
Table Thiiranes 3 Prepared in Solvent-Free Conditions
Entry
Ketone 1
Reaction Time MW
in min (oil bath in h)
Product 3
Rf a of 3
Yieldb,c MW
(oil bath),%
trans:cis ratiod
1
2
2.0 (14)
3.0 (12)
0.72
88 (46)
85 (43)
0.70 (0.67)
91:9
91:9
93:7
3
4
3.0 (12)
3.5 (15)
0.70 (0.67)
0.69 (0.65)
88 (45)
86 (40)
5
4.0 (15)
0.66 (0.63)
81 (39)
89:11
6
7
8
2.5 (13)
2.5 (11)
3.5 (14)
0.68
94 (49)
92 (41)
84 (40)
0.68
S
(0.71)
0:100
0:100
96:4
9
3.5 (14)
3.0 (14)
(0.71)
0.60
86 (44)
94 (47)
10
11
3.0 (14)
0.64
90 (43)
94:6
a TLC was carried out on Silica gel-G (hexane–EtOAc, 8:2).
b Yield of isolated and purified product.
c Known products (entries 1–9) were identified by comparison of their physical and 1H NMR spectral data with those reported in the litera-
ture.7,13,14
d Determined by 1H NMR spectroscopy of the crude products.13
Synthesis 2002, No. 16, 2344–2346 ISSN 0039-7881 © Thieme Stuttgart · New York

2346
L. D. S. Yadav, R. Kapoor
SHORT PAPER
MS: m/z = 240 (M+).
Anal. Calcd for C16H16S: C, 79.95; H, 6.71; S, 13.34. Found: C,
available -halo ketones employing microwave irradia-
tion technique in solvent-free conditions, which is envi-
ronmentally friendly and may be useful in organic 80.20; H, 6.53; S, 13.56.
synthesis.
cis-2,3-Bis(4-methylphenyl)thiirane
Mp 48–50 °C.
1H NMR (400 MHz): = 2.30 (Me), 3.25 (s, 2 H, SCH), 7.20–7.31
(m, 8 Harom).
13C NMR (100 MHz): = 21.16 (Me), 37.03 (SCH), 129.32,
129.42, 132.55, 136.96 (Carom).
An unmodified domestic microwave oven (Padmini Essentia, Mod-
el Brownie, operating at 2450 MHz) was used at an output of 600
W for all the experiments. Melting points were determined by open
glass capillary method and are uncorrected. IR spectra in KBr were
recorded on a Perkin-Elmer 993 IR spectrophotometer. NMR spec-
tra were recorded on a Bruker WM-40 C (400 MHz) FT spectro-
meter in CDCl3 using TMS as an internal reference. Mass spectra
were recorded on a JEOL D-300 mass spectrometer. All chemicals
used were reagent grade. Silica gel-G was used for TLC and silica
gel, Aldrich 100-200 mesh for column chromatography.
Anal. Calcd for C16H16S: C. 79.95; H. 6.71; S, 13.34. Found: C,
79.67; H, 6.56; S, 13.62.
MS: m/z = 240 (M+).
Substituted Thiiranes 3; General Procedure
Acknowledgment
Thoroughly mixed 1 (3.0 mmol), 2 (3.0 mmol) and freshly prepared
NaBH4-alumina10 (1.13 g, 3.0 mmol of NaBH4) were taken in a Pyr-
ex test tube, placed in an alumina bath inside the microwave oven
and irradiated for the specified time (Table). After completion of the
reaction, monitored by TLC (hexane–EtOAc, 8:2), the product was
extracted with CH2Cl2 (3 20 mL) and the extract was evaporated
under reduced pressure to leave the crude product 3 which was
found to be a diastereomeric mixture (trans:cis ratio as determined
We sincerely thank RSIC, Lucknow, India for providing microana-
lyses and spectra.
References
(1) For reviews, see: (a) Dittmer, D. C. Thiiranes and Thiirenes
In Comprehensive Heterocyclic Chemistry, Vol. 7;
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Carbon Compounds Vol. IV A; Sainsbury, A., Ed.; Elsevier
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Inc.: New York, 1964, 576.
(2) Dittmer, D. C. Thiiranes and Thiirenes In Comprehensive
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1
by H NMR spectroscopy13 is recorded in the Table). The crude
product was purified by silica gel column chromatography (hex-
ane–EtOAc, 8:2) to obtain an analytical sample of a single dia-
stereomer of 3 (Table).
trans-2,3-Bis(4-chlorophenyl)thiirane
Mp 94–96 °C.
1H NMR (400 MHz): = 3.83 (s, 2 H, SCH), 7.52–7.64 (m, 8
Harom).
13C NMR (100 MHz): = 39.54 (SCH), 128.72, 130.70, 133.21,
134.53 (Carom).
MS: m/z = 280 (M+).
Anal.Calcd for C14H10Cl2S: C, 59.80; H, 3.58; S, 11.40. Found: C,
59.52, H, 3.39; S, 11.68.
(6) Meyers, A. I.; Ford, M. E. J. Org. Chem. 1976, 41, 1735.
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cis-2,3-Bis(4-chlorophenyl)thiirane
Mp 71–73 °C.
1H NMR (400 MHz): = 3.31 (s, 2 H, SCH), 7.72–7.83 (m, 8
Harom).
13C NMR (100 MHz): = 37.01 (SCH), 128.76, 130.75, 133.26,
134.57 (Carom).
MS: m/z = 280 (M+).
Anal. Calcd for C14H10Cl2S: C, 59.80; H, 3.58; S,11.40. Found: C,
59.50; H, 3.69; S, 11.23.
trans-2,3-Bis(4-methylphenyl)thiirane
Mp 68–69 °C.
1H NMR (400 MHz): = 2.29 (s, 6 H, Me), 3.76 (s, 2 H, SCH),
7.14-7.26 (m, 8 Harom).
13C NMR (100 MHz): 21.13 (Me), 39.51 (SCH), 129.30, 129.41,
132.53, 136.94 (Carom).
Synthesis 2002, No. 16, 2344–2346 ISSN 0039-7881 © Thieme Stuttgart · New York