Iodine as a mild, efficient, and cost-effective catalyst for the synthesis of thiiranes from oxiranes

Article abstract of DOI:10.1007/s00706-008-0925-1

We developed an efficient protocol for the synthesis of thiiranes from oxiranes using a catalytic amount of molecular iodine. The notable features of this procedure are mild reaction conditions, high conversions, short reaction times, economic viability o

Full text of DOI:10.1007/s00706-008-0925-1

Monatsh Chem 139, 1363–1367 (2008)
DOI 10.1007/s00706-008-0925-1
Printed in The Netherlands
Iodine as a mild, efficient, and cost-effective catalyst for the synthesis
of thiiranes from oxiranes
Jhillu S. Yadav, Basi V. Subba Reddy, Sandip Sengupta, Manoj K. Gupta, Gakul Baishya,
Sukkala J. Harshavardhana, Uttam Dash
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad, India
Received 26 October 2007; Accepted 27 February 2008; Published online 9 June 2008
# Springer-Verlag 2008
Abstract We developed an efficient protocol for the
synthesis of thiiranes from oxiranes using a catalytic
amount of molecular iodine. The notable features of
this procedure are mild reaction conditions, high con-
versions, short reaction times, economic viability of
the reagents, compatibility with various functionali-
ties, and simple experimental=product isolation pro-
cedures which make it a useful and attractive process
for the synthesis of a range of thiiranes.
[4], silica gel supported potassium thiocyanate [5],
indium halides=KSCN [6] and polymeric cosolvent=
NH4SCN [7], together with solvent-free conditions
[8], ionic liquids [9], and several more [10, 11].
However, many of these methods often involve the
use of expensive or toxic reagents, the formation of
mixtures of products resulting in low yields, and
undesirable side reactions due to the rearrangement
or polymerization of the starting oxiranes. In spite of
a number of methods reported for the synthesis of
thiiranes, there is always a great demand in develop-
ing catalytic methods for high yielding protocols
using readily available and less expensive reagents.
Recently, molecular iodine has received consid-
erable attention as an inexpensive, non-toxic, and
readily available reagent for various organic trans-
formations, affording the corresponding products
with high selectivity in excellent yields [12–16].
The mild Lewis acidity associated with iodine has
led to its use in organic synthesis using catalytic to
stoichiometric amounts. However, there have been
no reports on the use of iodine for the synthesis of
thiiranes from oxiranes and ammonium thiocyante.
Keywords Oxiranes; Thiiranes; Iodine; Ammonium
thiocyanate.
Introduction
Thiiranes are important and useful building blocks
for the synthesis of polymers, pharmaceuticals,
pesticides, and herbicides [1]. Since organo-sulfur
compounds have become increasingly useful and
important in the field of drugs and pharmaceuticals,
the development of simple, convenient and effici-
ent approaches are desirable. As a result, numerous
methods have been reported to synthesize thiiranes
using a variety of reagents such as ꢀ-cyclodextrin=
thiourea [2], phosphine sulfide [3], N,N-dimethyl-
thioformamide in the presence of trifluoroacetic acid
Correspondence: Jhillu S. Yadav, Division of Organic Chem-
istry, Indian Institute of Chemical Technology, Hyderabad
500 007, India. E-mail: yadavpub@iict.res.in
Scheme 1

1364
J. S. Yadav et al.
Table 1 Iodine catalyzed synthesis of thiiranes from oxiranes
Entry
Oxiiranes
Thiiranesa
Time=h
Yield=%b
a
2.5
94
b
c
d
e
f
3.5
3.5
2.5
3.5
4.0
96
96
95
90
90
g
5.0
80
h
i
3.0
2.5
93
93
j
3.5
96
k
l
3.5
3.0
96
80
m
n
3.5
3.5
82
82
o
7.5
7.0
85
75
P
1
a All products were characterized by IR, H NMR spectra and mass spectrometry
b Isolated and unoptimized yields after column chromatography

Iodine as a mild, efficient, and cost-effective catalyst
1365
Results and discussion
In continuation of our interest in the catalytic ap-
plication of elemental iodine [17–19], we disclose
herein a mild, efficient, and practical methodology
for the synthesis of thiiranes from oxiranes and
ammonium thiocyanate using molecular iodine as a
catalyst. Initially, we attempted the reaction of 2-
(phenoxymethyl)oxirane (1, 1 eq.) with ammonium
thiocyante (2, 1.5 eq.) in the presence of 10 mol% of
elemental iodine in acetonitrile at room temperature.
The reaction went to completion in 2.5 h affording
thiirane 3a in 94% yield (Scheme 1).
The remarkable catalytic activity of molecular io-
dine provided the incentive for further study of reac-
tions with other epoxides. Interestingly, a variety of
epoxides reacted efficiently with ammonium thiocy-
anate to furnish the corresponding thiiranes in good
yields (entries b–p, Table 1). In addition, functiona-
lized oxiranes also worked well under these reaction
conditions without affecting the protecting groups
(entries e, i–p, Table 1, Scheme 2).
This method is compatible with substrates bearing
acid sensitive protecting groups such as THP, TBDMS,
benzyl, and methyl ethers (entries e, i–p, Table 1). This
procedure is also useful for the selective conversion of
an epoxide into a thiirane without affecting an acid
labile primary acetonide (entry p, Table 1).
The reaction may proceed via the activation of oxi-
rane by I2 followed by nucleophilic ring opening with
ꢀSCN and a subsequent formation of oxathiolanium
intermediate, which eventually undergoes a rearrange-
ment to thiirane (Scheme 3) [20]. However, most of
the existing methods failed to produce thiiranes from
oxiranes without the cleavage of THP, TBDMS ethers,
and acetonide [1]. The products thus obtained were
Scheme 2
characterized by 1H NMR, IR, and mass spectrometry.
In all cases, the reactions proceeded well in refluxing
acetonitrile and the products were obtained in relative-
ly high yields. To know the efficiency of elemental
iodine, we have carried out the experiments with some
reported catalysts and the comparative results are sum-
marized in Table 2. The scope and generality of this
process is illustrated in Table 1.
Experimental
Melting points were recorded on a Bu¨chi R-535 apparatus.
IR spectra were recorded on a Perkin-Elmer FT-IR 240-c
spectrophotometer using KBr optics. 1H NMR spectra were
recorded on a Varian-unity 300 spectrometer in CDCl3
using TMS as internal standard. Mass spectra were recorded
on a Finnigan MAT 1020 mass spectrometer operating at
70 eV.
General procedure for the synthesis of thiiranes
A mixture of 1 mmol oxiranes, 1.5 mmol ammonium thio-
cyanate, and 25 mg iodine (10 mol%) in 5 cm3 dry acetoni-
trile was stirred for a specified time (see Table 1). After
completion of the reaction as indicated by TLC, the solvent
was evaporated under vacuum and reaction mass was
quenched with 2 cm3 sat. ammonium thiosulphate and
extracted with 2ꢁ10 cm3 ethyl acetate. The combined or-
ganic layers were dried over anhydrous Na2SO4, concen-
trated in vacuo, and purified by column chromatography on
silica gel (Merck, 100–200 mesh, ethyl acetate:n-hexane,
1:9) to afford pure thiiranes. The products thus obtained
were characterized by their TLC, IR, NMR spectroscopy,
Scheme 3

1366
J. S. Yadav et al.
Table 2 A Comparative study for the synthesis of benzylox-
ymethylthiirane from benzyloxymethyloxirane
ꢂ ¼ 7.31–7.20 (m, 5H), 4.53 (d, J ¼ 0.9 Hz, 2H), 3.67 (ddd,
J ¼ 10.3, 5.4, 0.7 Hz, 1H), 3.38 (dd, J ¼ 10.3, 6.7Hz, 1H),
3.06–2.98 (m, 1H), 2.45 (td, J ¼ 6.2, 2.0, 0.9 Hz, 1H), 2.15
(dd, J ¼ 5.2, 1.1 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3):
ꢂ ¼ 32.5, 42.8, 71.8, 73.5, 127.9, 128.6, 130.1, 140.6ppm;
ESI=MS: m=z ¼ 181.0 [Mþ þ H], 102.1; HRMS (ESI): calcd
for C10H12ONaS 203.0506, found 203.0509.
Conversion Time Yielda
S.
No.
Catalyst
%
h
%
1
2
3
4
5
6
7
Oxalic acid (0.2 eq)
RuCl3 (0.05 eq)
91
95
90
92
92
98
96
2.0
0.5
2.0
2.5
1.0
0.5
2.5
85
90
89
90
90
95
94
SiO2–AlCl3 (0.1 eq)
Al(DS)3 ꢃ 3H2O (0.1 eq)
PVA and PAA=NaOH
TiO(TFA)2 or TiCl3(OTf)
Iodine (0.1 eq)
2-Phenylthiirane (3f, C8H8S)
Colorless liquid; IR (KBr): ꢁꢀmax ¼ 3061, 3029, 2924, 2852,
1492, 1453, 1071, 1040, 760, 695, 613 cmꢀ1 1H NMR
;
(CDCl3, 300 MHz): ꢂ ¼ 7.27–7.18 (m, 5H), 3.81 (t, J ¼
6.5 Hz, 1H), 2.80 (d, J ¼ 6.5 Hz, 1H), 2.56 (dd, J ¼ 5.0,
1.4 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3): ꢂ ¼ 35.2, 42.4,
125.1, 128.3, 130.2, 139.8ppm; FAB Mass: m=z ¼ 137
[Mþ þ H], 136.0; HRMS (ESI): calcd for C8H8NaS 159.0245,
found 159.0252.
a Yield refers to pure products after chromatography
and mass spectrometry. Data for 3e, 3g, 3h, and 3i are
identical with these in Refs. [2, 6, 21, 22].
2-[2-(Benzyloxy)-2-phenylethyl]thiirane (3j, C17H18OS)
Liquid; IR (KBr): ꢁꢀmax ¼ 3061, 3028, 2861, 1493, 1451,
2-(Phenoxymethyl)thiirane (3a, C9H10OS)
Colorless liquid; IR (KBr): ꢁꢀmax ¼ 3034, 2925, 2860, 1599,
1H NMR (CDCl3, 300 MHz): ꢂ ¼
1
1091, 783, 699 cmꢀ1
;
1495, 1241, 1036, 753 cmꢀ1; H NMR (CDCl3, 300 MHz):
ꢂ ¼ 7.26–7.19 (m, 2H), 6.93–6.82 (m, 3H), 4.23 (dd, J ¼
11.3, 6.4 Hz, 1H), 3.77 (dd, J ¼ 9.8, 7.5 Hz, 1H), 3.25–3.17
(m, 1H), 2.57 (dd, J ¼ 6.0, 1.5 Hz, 1H), 2.27 (d, J ¼ 6.0 Hz,
1H) ppm; 13C NMR (75 MHz, CDCl3): ꢂ ¼ 23.9, 31.3, 72.5,
114.6, 121.1, 129.5, 158.3 ppm; ESI=MS: m=z ¼ 189.9
[Mþ þ Na], 117.2; HRMS (ESI): calcd for C9H10ONaS
189.0350, found 189.0359.
7.36–7.14 (m, 10H), 4.53–4.39 (m, 2H), 4.31–4.21 (dd,
J ¼ 11.7, 8.8 Hz, 1H), 3.21–2.93 (m, 1H), 2.50–2.31 (m,
2H), 2.12–1.96 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3):
ꢂ ¼ 25.6, 31.9, 70.3, 81.2, 126.8, 127.6, 127.7, 127.9, 128.3,
128.5, 141.1, 141.6 ppm; ESI=MS: m=z ¼ 271 [Mþ þ H],
179.1; HRMS (ESI): calcd for C17H18ONaS 293.0976,
found 293.0971.
2-[2-(Benzyloxy)-2-cyclohexylethyl]thiirane (3k, C17H24OS)
Colorless liquid; IR (KBr): ꢁꢀmax ¼ 2925, 2852, 1449, 1098,
1068, 737, 697cmꢀ1; 1H NMR (CDCl3, 300MHz): ꢂ ¼ 7.42–
7.17 (m, 5H), 4.57 (d, J ¼ 3.6Hz, 1H), 4.48 (s, 1H), 3.39–3.21
(m, 1H), 3.08–2.82 (m, 1H), 2.52 (d, J ¼ 6.6 Hz, 1H), 2.40 (d,
J ¼ 5.8Hz, 1H), 2.20–1.88 (m, 2H), 1.83–1.55 (m, 6H), 1.42–
0.93 (m, 5H) ppm; 13C NMR (75 MHz, CDCl3): ꢂ ¼ 26.3,
26.8, 28.6, 28.9, 34.0, 38.6, 41.4, 72.7, 83.3, 127.7, 127.8,
128.2, 138.8 ppm; ESI=MS: m=z ¼ 277 [Mþ þ H], 278.1;
HRMS (ESI): calcd for C17H24ONaS 299.1445, found
299.1454.
2-[(2-Methylphenoxy)methyl]thiirane (3b, C10H12OS)
Colorless liquid; IR (KBr): ꢁꢀmax ¼ 2922, 2858, 1494, 1460,
1242, 1120, 1047, 1011, 750 cmꢀ1
;
1H NMR (CDCl3,
300 MHz): ꢂ ¼ 7.07 (t, J ¼ 7.5 Hz, 2H), 6.81 (t, J ¼ 7.5 Hz,
1H), 6.72 (d, J ¼ 8.3 Hz, 1H), 4.21 (dd, J ¼ 10.5, 5.2 Hz,
1H), 3.82 (dd, J ¼ 10.5, 7.5 Hz, 1H), 3.27–3.19 (m, 1H),
2.55 (d, J ¼ 6.0Hz, 1H), 2.28 (dd, J ¼ 5.2, 1.5 Hz, 1H), 2.23
(s, 3H) ppm; 13C NMR (75 MHz, CDCl3): ꢂ ¼ 16.1, 23.7,
31.5, 72.5, 111.4, 120.8, 126.6, 126.9, 130.7, 156.4 ppm;
ESI=MS: m=z ¼ 181 [Mþ þ H], 179; HRMS (ESI): calcd for
C10H12ONaS 203.0506, found 203.0510.
tert-Butyldimethyl(4-(thiiran-2-yl)butoxy)silane
(3l, C12H26OSiS)
2-[(2-Napthyloxy)methyl]thiirane (3c, C13H12OS)
White solid; mp 72ꢂC; IR (KBr): ꢁꢀmax ¼ 2923, 2854, 1627,
Liquid; IR (KBr): ꢁꢀmax ¼ 2932, 2858, 2363, 1731, 1467,
1595, 1463, 1389, 1256, 1216, 1182, 1045, 1005, 839,
1
1
1388, 1361, 1253, 1102, 1007, 837, 776, 662 cmꢀ1. H NMR
813, 741 cmꢀ1; H NMR (CDCl3 300 MHz): ꢂ ¼ 7.71–7.62
(CDCl3, 300 MHz): ꢂ ¼ 3.63–3.59 (m, 2H), 2.81–2.77 (m,
1H), 2.43 (d, J ¼ 6.0 Hz, 1H), 2.08 (d, J ¼ 6.0 Hz, 1H), 1.86–
1.82 (m, 2H), 1.60–1.51 (m, 4H), 0.88 (s, 9H), 0.33 (s, 6H)
ppm. ESI=MS: m=z ¼ 247 [Mþ þ H].
(m, 3H), 7.38 (t, J ¼ 7.5 Hz, 1H), 7.28 (t, J ¼ 8.3 Hz, 1H),
7.09 (dd, J ¼ 9.0, 2.2Hz, 1H), 7.05 (d, J ¼ 2.2 Hz, 1H), 4.33
(dd, J ¼ 9.8, 5.2Hz, 1H), 3.88 (dd, J ¼ 9.8, 7.5 Hz, 1H), 3.30–
3.22 (m, 1H), 2.58 (d, J ¼ 6.0 Hz, 1H), 2.30 (dd, J ¼ 5.2, 1.5 Hz,
1H) ppm; 13C NMR (75 MHz, CDCl3): ꢂ ¼ 23.9, 31.2,
72.4, 76.9, 106.8, 118.6, 123.7, 127.5, 129.0, 129.5, 134.3,
156.2 ppm; ESI=MS: m=z ¼ 217 [Mþ þ H], 197; HRMS
(ESI): calcd for C13H12ONaS 239.0506, found 239.0512.
2-(4-(Thiiran-2-yl)butoxy)-tetrahydro-2H-pyran
(3m, C11H20O2S)
Liquid; IR (KBr): ꢁꢀmax ¼ 2925, 2853, 2366, 1742, 1458,
1370, 1167, 1121, 1026 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
ꢂ ¼ 4.56–4.51 (m, 1H), 3.84–3.77 (m, 1H), 3.73–3.67 (m, 1H),
3.50–3.41 (m, 1H), 3.38–331 (m, 1H), 2.88–2.81 (m, 1H),
2.46 (d, J ¼ 6.7 Hz, 1H), 2.11 (d, J ¼ 5.2 Hz, 1H), 1.92–1.76
2-[(Benzyloxy)methyl]thiirane (3d, C10H12OS)
Liquid; IR (KBr): ꢁꢀmax ¼ 3028, 2923, 2855, 1452, 1368,
1249, 1092, 739, 697 cmꢀ1 1H NMR (CDCl3, 300 MHz):
;

Iodine as a mild, efficient, and cost-effective catalyst
1367
(m, 2H), 1.77–1.48 (m, 10H) ppm; ESI=MS: m=z ¼ 217
[Mþ þ H].
References
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and Thiiranes in Comprehensive Heterocyclic Chemistry,
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2-[3-(Benzyloxy)propyl]thiirane (3n, C12H16OS)
Colorless liquid; IR (KBr): ꢁꢀmax ¼ 2927, 2855, 1449, 1362,
1102, 740 cmꢀ1
;
1H NMR (CDCl3, 300 MHz): ꢂ ¼ 7.31–
7.18 (m, 5H), 4.43 (s, 2H), 3.46 (dt, J ¼ 8.0, 5.8, 2.1 Hz,
2H), 2.86–2.74 (dt, J ¼ 7.3, 5.8, 2.1 Hz, 1H), 2.39 (d, J ¼
6.5 Hz, 1H), 2.05 (d, J ¼ 6.5 Hz, 1H), 2.01–1.88 (m, 1H),
1.84–1.70 (m, 2H), 1.53–1.39 (m, 1H) ppm; 13C NMR
(75 MHz, CDCl3): ꢂ ¼ 35.6, 25.8, 29.3, 33.2, 69.4, 72.8,
128.2, 127.5, 127.4, 138.3 ppm; ESI=MS: m=z ¼ 231
[Mþ þ Na], 184.1; HRMS (ESI): calcd for C12H16ONaS
231.0819, found 231.0826.
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Tetrahedron Lett 45:7187
2-[2-(Methoxy)-2-phenylethyl]thiirane (3o, C11H14OS)
Liquid; IR (KBr): ꢁꢀmax ¼ 3061, 3027, 2983, 2930, 2856,
2821, 1453, 1356, 1237, 1191, 1100, 1048, 758, 701, 612,
1
561 cmꢀ1; H NMR (CDCl3, 300 MHz): ꢂ ¼ 7.35–7.21 (m,
5H), 4.27–4.18 (m, 1H), 3.23 (d, J ¼ 18.8 Hz, 3H), 3.14–
3.05 (m, 1H), 2.64–2.48 (m, 1H), 2.37–2.26 (m, 1H), 2.10–
2.01 (m, 2H) ppm; ESI=MS: m=z ¼ 217 [Mþ þ Na], 172,
74.1.
4-(1,2-bis(benzyloxy)-2-(thiiran-2-yl)ethyl)-2,2-dimethyl-
1,3-dioxolane (3p, C23H28O4S)
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Liquid; IR (KBr): ꢁꢀmax ¼ 3064, 3030, 2985, 2927, 1631, 1495,
1454, 1384, 1254, 1212, 1070, 856, 736, 698 cmꢀ1; 1H NMR
(CDCl3, 300 MHz): ꢂ ¼ 7.30–7.23 (m, 10H), 4.82–4.74 (m,
2H), 4.63–4.57 (m, 2H), 4.17 (dt, J ¼ 6.8, 4.5 Hz 1H), 3.97 (dt,
J ¼ 12.8, 8.3 Hz, 2H), 3.76–3.69 (m, 1H), 3.02 (dd, J ¼
8.3, 3.0 Hz, 1H), 2.95–2.88 (m, 1H), 2.09 (dd, J ¼ 6.0,
1.5 Hz, 1H), 1.95 (dd, J ¼ 5.2, 1.5 Hz, 1H), 1.39 (s, 3H),
1.29 (s, 3H) ppm; ESI=MS: m=z ¼ 423 [Mþ þ Na], 407.
Acknowledgements
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47:8471
SS, MKG, GB, SJH, and UD thank CSIR, New Delhi, for the
award of fellowships.