Microwave-mediated efficient protection of carbonyl compounds as 1,3-oxathiolanes in the presence of iodine under solvent free condition

Article abstract of DOI:10.1246/cl.2006.542

A mild, efficient, and solvent free protocol for conversion of aldehydes and ketones into their corresponding 1,3-oxathiolanes using 2-mercaptoethanol in the presence of catalytic amount of elemental iodine is reported. Copyright

Full text of DOI:10.1246/cl.2006.542

542
Chemistry Letters Vol.35, No.5 (2006)
Microwave-mediated Efficient Protection of Carbonyl Compounds as 1,3-Oxathiolanes
in the Presence of Iodine under Solvent Free Condition
Ghanashyam Bezꢀ and Nabajyoti Baruah
Department of Chemistry, Dibrugarh University, Dibrugarh-786004, Assam, India
(Received February 24, 2006; CL-060230)
A mild, efficient, and solvent free protocol for conversion of
R1
R1
R2
HO
O
aldehydes and ketones into their corresponding 1,3-oxathiolanes
using 2-mercaptoethanol in the presence of catalytic amount of
elemental iodine is reported.
I2 (5 mol %), µW
+
O
R2
solvent free
S
HS
Scheme 1.
Protection and deprotection of reactive functional groups in
organic compounds are very important strategies in multistep or-
ganic synthesis.1 Besides choosing the right protecting group
with optimum stability, selection of mild, and efficient catalyst
to affect these protection and deprotection also plays a pivotal
role in dictating the efficiency of a particular reaction protocol.
The anonymity in choosing the right catalyst with optimum effi-
ciency is being considered as one of the driving forces for the
synthetic chemists in their thrives for better reaction strategies
leading to ascending demands for newer discoveries.
Protection of carbonyl compounds as 1,3-oxathiolanes1 is
one of the most important protocols in organic synthesis because
of their easy introduction, greater stability towards acidic media
as compared to O,O-acetals and easier deprotection as compared
to corresponding S,S-acetals.2 Nonetheless, the oxathioacetals
find application as important starting materials for stereoselec-
tive synthesis of tertiary ꢀ-hydroxy aldehydes, ꢀ-hydroxy acids
and glycols, where they behave as acyl equivalent in the carbon–
carbon bond-forming reactions.3 Although the protection of
The efficiency of our method has been demonstrated through
the results documented in the Table 1. It has been observed that
both aliphatic and aromatic aldehydes (Entry 1–11) give reason-
ably good yield of 1,3-oxathiolanes except the citral (Entry 7), in
which case, significant amount of an unidentified by-product was
formed besides the desired product. Both cyclic and acyclic
ketones (Entry 12–20) gave very good yield of the desired 1,3-
oxathiolanes except the benzophenone (Entry 18) where in spite
of giving 20 min reaction time with 5.0 equivalents of 2-
mercaptoethanol could resulted only 30% of its 1,3-oxathiolane
derivative. The fact that m-acetoxybenzaldehyde (Entry 10) and
2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde (Entry 11) gener-
ate their corresponding oxathiolanes in very good yields suggest
that under this condition acid-sensitive functional groups remain
unaffected. Shi’s Ketone (Entry 21) was recovered intact even
after 8 h of reaction.
The substrate catalyst ratio was determined by studying the
extent of conversion, when p-chlorobenzaldehyde was treated
with 2-mercaptoethanol in the presence of different30 amount of
iodine. In order to study the chemoselectivity of our method, 3-
oxobutanal was treated with 2-mercaptoethanol (1 equiv.) under
similar reaction condition for 1 h. It was observed that the alde-
hyde group was protected as 1,3-oxathiolane in preference to the
ketonic functionality (Scheme 2).
carbonyls as 1,3-oxathiolanes can be accomplished by using
HCl,4 HClO4,5 BF3 Et2O, TMSCl–NaI,7 p-TsOH,8 LiBF4,9
6
.
Bu4NBr3,11 TMSOTf,12 i-Pr3SiOTf,13
10
.
BF3 Et2O–CaCl2,
SO2,14 ZnCl2–Na2SO4,15 ZrCl2,16 [(dppb)Pt(m-OH)]2(BF4)2–
Mg(ClO4)2 2H2O, polystyryldiphenylphosphonium iodide,18
17
.
natural kaolinitic clay,19 KSF,20 Amberlyst-15,21 PPA on
silica,22 Yb(OTf)3 in ionic liquid,23 bromodimethylsulphonium
bromide,24 and Fe(III) flouride25 many of them suffers from
the difficulties such as longer reaction time, harsh reaction
condition, incompatibility with acid sensitive functional groups,
removal of azeotropic mixture, use of dehydrating reagent,
involvement of expensive and moisture sensitive catalysts, etc.
Organic reactions under solvent free condition26 have in-
creasingly become popular from the viewpoint of Green chem-
istry.27 In recent times, microwave-accelerated reactions under
solvent free conditions are getting increasing attention.28 There-
fore, efforts are being made to find a reagent system that would
be environmentally benign and clean and yet mild, efficient, se-
lective, operationally simple, and cost effective. Herein, we wish
to report an efficient method for protection of aldehyde and ke-
tones as 1,3-oxathiolanes by reaction with 2-mercaptoethanol in
presence of catalytic amount of molecular iodine (Scheme 1).
Although the reaction gives almost similar yield on heating with
acetonitrile, microwave irradiation at power 100 W, and in the
absence of any solvent visibly reduces the reaction time and
the amount of iodine required.29
Typically, a mixture of methyl acetoacetate (0.232 g, 2
mmol), 2-mercaptoethanol (0.234 g, 3 mmol), and iodine
(0.026 g, 0.1 mmol) was taken in a 50 mL oven-dried Erlen-Mey-
er flask and irradiated with microwave at 100 W. After 4 min, the
reaction was quenched by adding 5% aqueous Na2S2O3 solution
(5 mL) and extracted with diethyl ether (3 ꢁ 25 mL). The ethere-
al layer was dried over anhydrous Na2SO4, concentrated and pu-
rified by column chromatography (2% ethyl acetate in hexane) to
get the pure product in 80% (0.282 g, 1.6 mmol) yield (Entry 19).
IR (neat, cmꢂ1): 1045, 1735; 1H NMR (400 MHz, CDCl3): ꢁ
1.78 (s, 3H), 2.92 (s, 2H), 3.07 (t, J ¼ 5 Hz, 2H), 3.67 (s, 3H),
4.18 (t, J ¼ 5 Hz, 2H); MS: m/z 176, 161, 117, 103, 85, 69, 59.
In contrast to the previous methods, which required stoichio-
metric amount of the catalyst,10,14,15,18 in our method only
5 mol % is enough for completion of the reaction. Moreover,
O
O
O
HO
CHO+
HS
I2 (5 mol %)
µW
(1 equiv.)
S
Scheme 2.
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.5 (2006)
543
Table 1. Iodine-catalyzed formation of 1,3-oxathiolanes
4
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Org. Chem. 1968, 33, 2133. b) L. F. Fieser, J. Am. Chem.
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1970, 35, 2716. c) C. Djerassi, M. Gorman, J. Am. Chem.
Soc. 1953, 75, 3704.
Yield
Reaction time
/mina
Entry
Substrate
/%b
83
1
2
PhCHO
p-CH3C6H4CHO
3
3
81
5
6
3
p-ClC6H4CHO
3
84
4
5
p-NO2C6H4CHO
p-OH C6H4CHO
3
5
87
73
6
7
8
9
p-OMeC6H4CHO
Citral
3
5
5
3
89
59c
82
86
7
8
n-Octanal
m-(CO2Me)C6H4CHO
10
11
m-AcO C6H4CHO
3
4
91
80
O
CHO
9
J. S. Yadav, B. V. S. Reddy, S. K. Pandey, Synlett 2001, 238.
O
10 E. Fujita, Y. Nagao, K. Kaneko, Chem. Pharm. Bull. 1978,
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11 E. Mondal, P. R. Sahu, G. Bose, A. T. Khan, Tetrahedron
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hedron Lett. 1995, 36, 2285.
13 L. Streinz, B. Koutek, D. Saman, Collect. Czech. Chem.
Commun. 1997, 62, 665.
12
p-Bromoacetophenone
Acetophenone
4
92
13
14
15
5
3
3
81
95
92
Cyclohexanone
Cyclopentanone
16
17
18
Menthone
Carvone
Benzophenone
3
4
20
86
76
30d
19
20
21
Methyl acetoacetate
Cholestanone
4
80
14 B. Burczyk, Z. Kortylewicz, Synthesis 1982, 831.
15 J. Romo, G. Rosenkranz, C. Djerassi, J. Am. Chem. Soc.
1951, 73, 4961.
5
78
NRe
O
O
10
O
O
O
O
16 B. Karimi, H. Seradj, Synlett 2000, 805.
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621.
18 R. Caputo, C. Ferreri, G. Palumbo, Synthesis 1987, 386.
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G. Satori, Synthesis 2001, 1826.
22 T. Aoyama, T. Takido, M. Kodmari, Synlett 2004, 2307.
23 A. Kumar, N. Jain, S. Rana, S. M. S. Chauhan, Synlett 2004,
2785.
24 B. P. Bandgar, V. T. Kamble, A. Kulkarni, Aust. J. Chem.
2005, 58, 607.
aMicrowave irradiation was done with Samsung microwave,
Model-1630N keeping the power at 100 W. Yield of the pure
isolated product. Another unidentified product was observed.
d5.0 equiv. of 2-mercaptoethanol was used. eNR = No reaction.
b
c
neither the azeotropic removal of water4a,8a–8c,14 nor the use of
dehydrating agent10,15,17 is necessary in our methodology.
In conclusion, we have reported an efficient, simple straight-
forward, and chemoselective protocol for the synthesis of 1,3-
oxathiolanes from carbonyl compounds using iodine. Non-re-
quirement of solvent, dehydrating agent, anhydrous atmosphere,
and tedious removal of water during the reaction and the com-
patibility of the catalyst with acid sensitive fuctional groups such
as acetyl, nitro, methoxy, carbomethoxy, 1,3-dioxolane, etc. may
work wonder in multistep synthesis.
25 A. T. Khan, P. R. Sahu, A. Majee, J. Mol. Catal. A: Chem.
2005, 226, 207.
26 K. Tanaka, F. Toda, Chem. Rev. 2000, 100, 1025.
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J. C. Warner, Oxford University Press, Oxford, 1998.
28 a) D. Laskar, D. Prajapati, J. S. Sandhu, J. Chem. Res., Syn-
op. 2001, 313. b) G. L. Kad, V. Singh, K. P. Kaur, J. Singh,
Indian J. Chem. 1998, 37B, 172.
Authors are grateful to Vice-Chancellor, Dibrugarh Univer-
sity for providing the facility to work. Thanks are also to Dr.
Nabin C Barua, Dy Director, RRL, Jorhat, India for his valuable
helps and advice.
References and Notes
29 When p-chlorobenzaldehyde in acetonitrile was treated
with 2-mercaptoethanol in the presence of 2 mol % I2 at
room temperature, reaction did not complete even after
24 h and gave only 46% yield, while use of 5 mol % I2 gave
75% yield after 8 h. Use of 10 mol % of I2 gave 85% of the
desired product within half an hour.
30 2 mol % iodine could not complete the reaction even after
10 min and gave only 52% yield, while 10 mol % iodine does
not reduce the reaction time than the use of 5 mol % iodine,
where the conversion was complete within 3 min to give
84% of the desired product.
1
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2
3
Published on the web (Advance View) April 22, 2006; DOI: 10.1246/cl.2006.542