An efficient and novel method for the synthesis of sulfinate esters under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2006.02.080

The present letter describes a reliable one-stage process for the preparation of sulfinate esters from the corresponding sulfinic acid and alcohols in the presence of N,N′-dicyclohexylcarbodiimide (DCC) under solvent-free conditions.

Full text of DOI:10.1016/j.tetlet.2006.02.080

Tetrahedron Letters 47 (2006) 2717–2719
An efficient and novel method for the synthesis of sulfinate
esters under solvent-free conditions
b
b
Abdol R. Hajipour,a,b, Ali R. Falahati and Arnold E. Ruoho
*
aPharmaceutical Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan 84156, Iran
bDepartment of Pharmacology, University of Wisconsin Medical School, 1300 University Avenue, Madison, WI 53706-1532, USA
Received 21 January 2006; revised 15 February 2006; accepted 15 February 2006
Available online 3 March 2006
Abstract—The present letter describes a reliable one-stage process for the preparation of sulfinate esters from the corresponding
sulfinic acid and alcohols in the presence of N,N0-dicyclohexylcarbodiimide (DCC) under solvent-free conditions.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
of DCC under solvent-free conditions. This method
would be widely applicable as a general method for
the synthesis of alkyl sulfinate esters.
Reaction of organometallic reagent with a diastereomer-
ically pure sulfinate ester of menthol continues to be the
method that is most often employed for the preparation
of optically active sulfoxides.1 Despite recent advance-
ment in the asymmetric oxidation of sulfides to sulf-
oxides,2 the requisite sulfinate esters are generally
prepared from the corresponding sulfinic acids either
directly3 or via the sulfinyl chlorides.4 Alternatively, the
sulfinyl chloride may be directly prepared from a more
available disulfide, by reaction with chlorine5 or sulfuryl
chloride in the presence of acetic acid.6 The most com-
monly used methods are the reaction of sulfinyl chlorides
with alcohols in the presence of triethylamine or pyri-
dine7 and sodium sulfinates with chlorocarbonates in
alcohols.8 Other methods including alkylation of sulfinic
acids are also known,9–11 a useful one-step synthesis of
alkyl tert-alkansulfinates was reported.12
2. Results and discussion
The process in its entirety involves a simple mixing of
sulfinic acid and alcohols in the presence of DCC in a
mortar and grinding the mixture for the time specified
in Table 1 at room temperature. This method is very fast
and purification of product is straightforward (Scheme
1). The diastereoselectivity of products when we use
optical pure L-menthol was determined by 1H NMR
analysis on the crude reaction products. The diastereose-
lectivity was between 70:30 and 90:10; the products have
been characterized by 1H NMR, mass spectroscopy and
CHN analysis. The products were usually isolated in
excellent yield, and excellent diastereoselectivity and
short reaction time (Table 1). In all cases, the major dia-
stereomer is that with the more upfield methane, and
when separation was possible, the major diastereomer
in all cases proved to have a negative sign of rotation,
indicating the S configuration at sulfur.20,21
Reactions under solvent-free conditions have recently
attracted attention.13–15 The advantage of these methods
over conventional classical method is that they are clea-
ner reactions, have decreased reaction time, and easier
workup. In continuation of our ongoing program to
develop environmentally benign methods under solvent-
free conditions,16–19 we now wish to report a convenient
one-step method for the preparation of sulfinate esters,
starting from sulfinic acid and alcohols in the presence
In conclusion, the discovery of this efficient method
promises to find widespread application in the prepara-
tion of chiral sulfinate esters for which the correspond-
ing sulfinyl chlorides are thermally unstable and
sensitive to moisture. This technique should allow a
more rapid and complete screening of sulfur constituent
effects in chiral sulfoxide chemistry than has previously
been possible. This methodology is superior from the
Keywords: DCC; Solvent-free; Sulfinic acid; Sulfinate esters.
*
Corresponding author. Fax: +98 311 391 2350; e-mail: haji@
cc.iut.ac.ir
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.02.080

2718
A. R. Hajipour et al. / Tetrahedron Letters 47 (2006) 2717–2719
Table 1. Preparation of sulfinate estersa
2. (a) Pitchene, P.; KaganH, B. Tetrahedron Lett. 1984, 23,
1049; (b) Petchene, P.; Dunach, E.; Deshmulch, M. N.;
Laynn, H. D. J. Am. Chem. Soc. 1984, 106, 8188.
3. Boar, R. B.; Puter, A. C. Synthesis 1982, 584.
4. Harpp, D. N.; Friedlander, B. T.; Larsen, C.; Steliou, K.;
Stockton, A. J. Org. Chem. 1987, 43, 348.
5. Douglass, I. B.; Nuton, R. V. J. Org. Chem. 1968, 33,
2104.
6. Youn, J. H.; Herrmann, R. Synthesis 1987, 72.
7. Phillipe, H. J. Chem. Soc. 1925, 2552.
8. Yamamoto, A.; Kobayshi, M. Bull. Chem. Soc. Jpn. 1966,
39, 1292.
9. Wilt, J. W.; Stein, R. G.; Wagner, W. J. J. Org. Chem.
1967, 32, 2097.
10. Ott, R.; Rossing, A. Ber. Dtsch. Chem. Ges. 1885, 18,
2493.
11. Kobayshi, M. Bull. Chem. Soc. Jpn. 1966, 39, 1296.
12. Mikolajczyk, M.; Darbowicz, J. Synthesis 1974, 124.
13. (a) Gedye, R. J.; Westaway, K.; Ali, H.; Baldisera, L.;
Laberge, L.; Rousell, J. Tetrahedron Lett. 1986, 27, 279;
(b) Giguere, R. J.; Bray, T. L.; Duncan, S. M.; Majetich,
G. Tetrahedron Lett. 1986, 27, 4945.
14. (a) Abramovitch, A. Org. Prep. Proc. Int. 1991, 23, 685;
(b) Migos, D. M. P.; Baghurst, D. R. Chem. Soc. Rev.
1991, 20, 1; (c) Caddick, S. Tetrahedron 1995, 51,
10403.
Entry Ar
R
Reaction
time (min) (%)
Yield
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
p-CH3C6H4
CH3
CH3CH2
2
4
4
4
5
5
10
5
10
8
4
85
95
95
90
85
98
90
95
89
95
85
98
87
64
88
85
80
88
86
89
92
87
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
C6H5
CH3(CH2)2
CH3(CH2)3
CH3CH(CH3)CH2
CH3(CH2)2CH(CH3)
Cyclohexyl
C6H5CH2
C6H5CH2CH2
L-Menthyl
ClCH2CH2
CH3(CH2)6CH2
1-Adamantanyl
(CH3)3C
C6H5(CH2)4
p-MeOC6H4CH2
m-MeOC6H4CH2
p-ClC6H4CH2
Me
4
10
12
5
5
8
6
6
10
12
15
P-MeOC6H4 L-Menthyl
P-ClC6H4
P-tBuC6H4
L-Menthyl
L-Menthyl
a All products were identified by spectroscopy data (IR, NMR, mass
and CHN analysis).17–20,22,23
15. Loupy, A.; Petit, A.; Ramdiani, M.; Yvanaeff, C.; Maj-
doub, M.; Labiad, B.; Villemin, D. Can. J. Chem. 1993, 71,
90.
16. (a) Hajipour, A. R.; Arbabian, M.; Ruoho, A. E. J. Org.
Chem. 2002, 67, 8622; (b) Hajipour, A. R.; Ruoho, A. E.
Org. Prep. Proced. Int. 2002, 34, 647; (c) Hajipour, A. R.;
Mazloumi, G. Synth. Commun. 2002, 32, 23; (d) Hajipour,
A. R.; Ruoho, A. E. J. Chem. Res. (S) 2002, 547; (e)
Hajipour, A. R.; Adibi, H.; Ruoho, A. E. J. Org. Chem.
2003, 68, 4553; (f) Hajipour, A. R.; Bageri, H.; Ruoho, A.
E. Bull. Korean Chem. Soc. 2004, 25, 1238; (g) Hajipour,
A. R.; Malakutikhah, M. Org. Prep. Proced. Int. 2004,
364, 647; (h) Hajipour, A. R.; Ruoho, A. E. Sul. Lett.
2002, 25, 151; (i) Hajipour, A. R.; Mirjalili, B. F.; Zarei,
A.; Khazdooz, L.; Ruoho, A. E. Tetrahedron Lett. 2004,
45, 6607.
O
O
DCC
+ ROH
S
S
Solvent-free
Ar
OH
Ar
OR
Scheme 1.
point of view of yield, diastereoselectivity, lower reac-
tion time and the easier workup to the reported
methods.
17. (a) Hajipour, A. R.; Mallakpour, E.; Imanzadeh, G. J.
Chem. Res. 1999, 228; (b) Hajipour, A. R.; Mallakpour,
E.; Adibi, H. Chem. Lett. 2000, 460; (c) Hajipour, A. R.;
Mallakpour, E.; Afrousheh, A. Tetrahedron 1999, 55,
2311; (d) Hajipour, A. R.; Islami, F. Ind. J. Chem. 1999,
38B, 461; (e) Hajipour, A. R.; Mallakpour, E.; Imanzadeh,
G. Chem. Lett. 1999, 99; (f) Hajipour, A. R.; Hanteh-
zadeh, M. J. Org. Chem. 1999, 64, 8475; (g) Hajipour, A.
R.; Mallakpour, E.; Backnejad, H. Synth. Commun. 2000,
30, 3855; (h) Hajipour, A. R.; Mallakpour, E.; Afrousheh,
A. Phosphorus Sulfur Silicon 2000, 160, 67; (i) Hajipour,
A. R.; Mallakpour, E.; Khoee, S. Synlett 2000, 740; (j)
Hajipour, A. R.; Mallakpour, E.; Khoee, S. Chem. Lett.
2000, 120; (k) Hajipour, A. R.; Baltork, I. M.; Nikbaghat,
K.; Imanzadeh, Gh. Synth. Commun. 1999, 29, 1697.
18. (a) Hajipour, A. R.; Mahboubkhah, N. J. Chem. Res. (S)
1998, 122; (b) Hajipour, A. R.; Mallakpour, E.; Adibi, H.
Chem. Lett. 2000, 460; (c) Hajipour, A. R.; Mallakpour,
E.; Khoee, S. Chem. Lett. 2000, 120; (d) Hajipour, A. R.;
Mallakpour, E.; Khoee, S. Synlett 2000, 740; (e) Hajipour,
A. R.; Ruoho, A. E. Org. Prep. Proced. Int. 2005, 37, 298;
(f) Hajipour, A. R.; Ruoho, A. E. Org. Prep. Proced. Int.
2005, 37, 279.
Acknowledgements
We gratefully acknowledge the funding support received
for this project from the Isfahan University of Technol-
ogy (IUT), IR Iran (A.R.H.) and Grants GM 033138,
MH 065503, NS 033650 (A.E.R.) from the National
Institutes of Health, USA. Further financial support
from Center of Excellency in Chemistry Research
(IUT) is gratefully acknowledged.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2006.
02.080.
References and notes
1. (a) Anderson, K. K.; Gaffield, W.; Papanikolau, N. E.;
Foleg, J. W.; Perkins, R. I. J. Am. Chem. Soc. 1964, 86,
5637; (b) Drabowicz, J.; Bujnicki, B.; Mikaasezyk, M.
J. Org. Chem. 1982, 47, 3352.
19. Hajipour, A. R.; Kooshki, B.; Ruoho, A. E. Tetrahedron
Lett. 2005, 46, 5503.
20. Axelrod, M.; Bickar, P.; Jacobus, J.; Green, M. M.;
Mislow, K. J. Am. Chem. Soc. 1964, 90, 4835.

A. R. Hajipour et al. / Tetrahedron Letters 47 (2006) 2717–2719
2719
21. Typical experimental procedure: A mortar was charged
with the alcohol (1 mmol), p-toluenesulfinic acid (1 mmol,
0.16 g), and DCC (1 mmol, 0.21 g). The reaction mixture
was ground with a pestle in the mortar for the time
specified in Table 1. When TLC showed no remaining
toluenesulfinic acid (EtOAc/n-hexane, 15:85), to the reac-
tion mixture was added H2O (5 ml) and extracted with
ether (2 · 10 ml) and the combined ethereal layer was
washed with saturated NaHCO3, dried (MgSO4) and the
ether was evaporated to dryness using a rotary evaporator.
The residue was purified by column chromatography using
silica gel and a mixture of n-hexane/EtOAc (85:15) to give
the pure product.
22. See Supplementary data for experimental details.
23. Klunder, J. M.; Sharpless, K. B. J. Org. Chem. 1987, 52,
2598.