Facile polyethylene glycol (PEG-400) promoted synthesis of β-ketosulfones

Article abstract of DOI:10.1016/j.tetlet.2006.03.181

An efficient and convenient synthesis of β-ketosulfones is described. Reaction of an α-haloketone with sodium alkyl/aryl sulphinate yields the corresponding β-ketosulfone promoted by polyethylene glycol (PEG-400) as an efficient reaction medium.

Full text of DOI:10.1016/j.tetlet.2006.03.181

Tetrahedron Letters 47 (2006) 3853–3856
Facile polyethylene glycol (PEG-400) promoted
synthesis of b-ketosulfonesI
N. Suryakiran, T. Srikanth Reddy, K. Ashalatha, M. Lakshman and Y. Venkateswarlu*
Organic Chemistry Division-I, Natural Products Laboratory, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 22 February 2006; revised 22 March 2006; accepted 29 March 2006
Available online 27 April 2006
Abstract—An efficient and convenient synthesis of b-ketosulfones is described. Reaction of an a-haloketone with sodium alkyl/aryl
sulphinate yields the corresponding b-ketosulfone promoted by polyethylene glycol (PEG-400) as an efficient reaction medium.
Ó 2006 Elsevier Ltd. All rights reserved.
Among sulfur containing compounds, b-ketosulfones
are an important group of intermediates1 in Michael
and Knoevenagel reactions,2,3 and are valuable precur-
sors in the synthesis of acetylenes, allenes, chalcones,4–9
vinylsulfones10 and polyfunctionalized 4H-pyrans.11 b-
Ketosulfones are useful for the synthesis of ketones by
facile reductive elimination of the sulfone group12 and
also in the preparation of epoxy sulfones.13 In addition,
b-ketosulfones are precursors for optically active b-
hydoxysulfones.14 Although several methods for their
synthesis15–24 and their chemical reactions25,26 have been
reported in the literature, most are associated with long
reaction times, tedious reaction conditions and low
yields. Hence, there is a need for a rapid and efficient
method for the synthesis of b-ketosulfones.
and their inexpensive and eco-friendly nature. In this
connection, we report a synthesis of b-ketosulfones in
the presence of polyethylene glycol (PEG-400) as an effi-
cient reaction medium.
Reaction of sodium p-toluenesulphinate with a phenacyl
bromide/phenacyl chloride in refluxing ethanol for
10–12 h resulted in the formation of the corresponding
b-ketosulfone in 50% yield. However, when we carried
out the reaction in polyethylene glycol (PEG-400), the for-
mation of p-toluenesulfonylacetophenone, that is, b-keto-
sulfone 3 (Scheme 1), was complete in 10 min in 96% yield.
Encouraged by the speed of the reaction, various a-halo-
ketones were reacted with sodium alkyl/aryl sulphinates
in PEG-400 to yield b-ketosulphones 3 in excellent yields.
The reaction is facile even with hindered a-haloketones,
such as those in entries 13 and 17 in Table 2. In order to
compare the rate of the reaction in PEG-400, we carried
out the reaction in different solvents (Table 1). The poor
Polyethylene glycol promoted reactions27 have attracted
the attention of organic chemists due to their ease of
workup, the ability to act as phase transfer catalysts
O
O
O
S
SO2Na
X
PEG-400
rt
+
R2
R
R2
R
O
R1
R1
3
1
X = Cl, Br
2
Scheme 1.
Keywords: Polyethylene glycol (PEG-400); b-ketosulfones; a-haloketone; Sodium alkyl/aryl sulphinate.
q IICT Communication No. 060318.
*
Corresponding author. Tel.: +91 40 27193167; fax: +91 40 27160512; e-mail: luchem@iict.res.in
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.181

3854
N. Suryakiran et al. / Tetrahedron Letters 47 (2006) 3853–3856
Table 1. Solvent effect on the reaction of phenacyl bromide with sodium p-toluenesulphinate at room temperature
Entry
Solvent
Time
Yield (%)
1
2
3
4
5
6
7
8
PEG
PEG/CH3CN (1:1)
EtOH
CH3CN
IPA
C6H6
10 min
10 min
24 h
24 h
24 h
24 h
24 h
24 h
96
95
50
49
40
Nil
Nil
Nil
CHCl3
DCM
yields in hydroxylic and less polar solvents are probably
due to the lower solubilities of the sulphinate salt in these
solvents, coupled with the fact that the nucleophile
ðPhSO2ꢀÞ is solvated in hydroxylic solvents, thereby
reducing its effective nucleophilicity. It was observed that
in PEG-400 the reaction was complete with very fast times
and in excellent yields (Scheme 1, Table 2).
Typical experimental procedure (Scheme 1): A mixture
of the sodium alkyl/aryl sulphinate (1.1 mmol) and the
a-haloketone (1 mmol) was taken in 10 ml of polyethyl-
ene glycol, and stirred at rt for the appropriate time (see
Table 2). After completion of the reaction, as monitored
by TLC, the reaction mass was poured into water and
extracted into ethyl acetate. The organic layer was re-
moved under reduced pressure, and the crude product
was purified by column chromatography or crystallized
from methanol. The PEG was recovered from the aque-
ous layer and reused without loss of activity.
In conclusion, we have disclosed an inexpensive, fast and
efficient synthesis of b-ketosulfones using polyethyl
ethlylene glycol 400 as the reaction medium.
Table 2. Synthesis of b-ketosulfones by using polyethylene glycol (PEG-400) as an efficient reaction medium at room temperature
Entry
a-Haloketone
Sodium alkyl/aryl sulphinate
Product
Time (min)
Yielda (%)
96
O
S
O
SO2Na
O
10
Br
1
O
SO2Na
O
S
O
O
O
O
Br
2
3
4
10
30
10
95
80
95
O
CH3
CH3
O
S
Br
O
CH3SO2Na
CH3
O
O
O
S
SO2Na
SO2Na
Br
O
H3C
H3C
O
S
O
O
O
Br
Br
5
6
10
10
90
95
O
H3C
HO
H3C
HO
CH3
CH3
O
S
O
SO2Na
O
SO2Na
O
S
O
O
Br
7
8
10
10
93
93
O
CH3
HO
Cl
HO
Cl
CH3
SO2Na
O
S
O
O
Br
O
CH3
CH3

N. Suryakiran et al. / Tetrahedron Letters 47 (2006) 3853–3856
3855
Table 2 (continued)
Entry
a-Haloketone
Sodium alkyl/aryl sulphinate
Product
Time (min)
10
Yielda (%)
94
O
S
O
O
SO2Na
Br
9
O
Cl
Cl
O
S
O
O
SO2Na
Br
10
10
10
95
90
O
SO2Na
CH3
O
S
O
O
O
Br
Br
11
O
CH3
O
S
O
12
13
CH3SO2Na
10
10
92
90
CH3
O
SO2Na
O
S
O
O
Br
O
CH3
CH3
CH3
CH
3
O
S
SO2Na
O
O
O
O
14
15
16
10
10
10
95
95
95
Br
Br
Br
Br
H3C
H3C
H3C
H3C
H3C
O
SO2Na
O
S
O
O
CH3
CH3
O
S
O
CH3SO2Na
H3C
CH3
O
SO2Na
O
S
O
O
17
30
90
O
CN
CN
CH3
CH3
a Isolated yields after column chromatography/crystallization and all products gave satisfactory spectral and analytical data.
7. Looker, J. J. J. Org. Chem. 1966, 31, 2714.
Acknowledgements
8. Sengupta, S.; Sarma, D. S.; Mondal, S. Tetrahedron 1998,
54, 9791.
9. Sengupta, S.; Sarma, D. S.; Mondal, S. Tetrahedron:
Asymmetry 2001, 12, 513.
The authors thank Director IICT and CSIR for the
financial support.
10. Sengupta, S.; Sarma, D. S.; Mondal, S. Tetrahedron:
Asymmetry 1998, 9, 2311.
11. (a) Marco, J. L.; Fernandez, I.; Khiar, N.; Fernandez, P.;
Romero, A. J. Org. Chem. 1995, 60, 6678; (b) Marco, J. L.
J. Org. Chem. 1997, 62, 6575.
12. (a) Corey, E. J.; Chavosky, M. J. Am. Chem. Soc. 1964,
86, 1639; (b) Trost, B. M.; Arndt, H. C.; Strege, P. E.;
Verhowever, T. R. Tetrahedron Lett. 1976, 27, 3477; (c)
Kurth, M. J.; Brien, M. J. J. Org. Chem. 1985, 50, 3846;
(d) Fuju, M.; Nakamura, K.; Mekata, H.; Oka, S.; Ohno,
A. Bull. Chem. Soc. Jpn. 1988, 61, 495; (e) Guo, H.;
Zhang, Y. Synth. Commun. 2005, 30, 2564.
References and notes
1. Simpkins, N. S. In Sulfones in Organic Synthesis; Baldwin,
J. E., Ed.; Pergamon Press: Oxford, 1993.
2. Macro, J. L.; Fernandez, I.; Khira, N.; Fernandez, P.;
Romero, A. J. Org. Chem. 1995, 60, 6678.
3. Reddy, M. V. R.; Reddy, S. Acta Chim. Hung. 1984, 115, 269.
4. Ihara, M.; Suzuki, S.; Taniguchi, T.; Tokunaga, Y.;
Fukumoto, K. Tetrahedron 1995, 51, 9873.
5. Baldwin, J. E.; Adlington, R. M.; Crouch, N. P.; Hill,
R.L.; Laffeg, T. G. Tetrahedron Lett. 1995, 36, 7925.
6. Reddy, M. V. R.; Reddy, S. Acta Chim. Hung. 1985, 120, 275.
13. Trost, B. M. In Comprehensive Organic Chemistry; Perg-
amon Press, 1993; Vol. 1, p 530.

3856
N. Suryakiran et al. / Tetrahedron Letters 47 (2006) 3853–3856
14. (a) Svatos, A.; Hun Kova, Z.; Kren, V.; Hoskovec, M.;
Saman, D.; Valterova, I.; Vrkoc, J.; Koutek, B. Tetra-
hedron: Asymmetry 1996, 7, 1285; (b) Betus, P.; Phansav-
ath, P.; Vidal, V. R.; Genet, J. P.; Touati, A. R.; Homri,
T.; Hassine, B. B. Tetrahedron: Asymmetry 1999, 10, 1369;
(c) Gotor, V.; Rebolledo, F.; Liz, R. Tetrahedron: Asym-
metry 2001, 12, 513.
15. (a) Schank, K.; Weber, A. Synthesis 1970, 367; (b) Schank,
K. Annalen 1967, 75, 702.
16. Julia, M.; Paris, J. M. Tetrahedron Lett. 1973, 14, 4833.
17. Durst, T. In Comprehensive Organic Chemistry; Barton, D.
H. R., Ollis, W. D., Eds.; Peragmon Press: Oxford, UK,
1979; Vol. 4, Chapter 11.8, p 174.
20. Holmquist, C. R.; Roskamp, E. J. Tetrahedron Lett. 1992,
33, 1131.
21. Kamigata, N.; Udodaira, K.; Shimizu, T. J. Chem. Soc.,
Perkin Trans. 1. 1997, 783.
22. Field, L.; Lawson, J. E.; Mc Fenland, J. W. J. Am. Chem.
Soc. 1956, 78, 4389.
23. Kartrizky, A. R.; Ashraf, A. A.; Fattah, A.; Mingyiwang
J. Org. Chem. 2003, 68, 1443.
24. Grossert, J. S.; Dubey, P. K.; Gill, G. H.; Stancey, T.;
Cameron, S. T.; Patric, A. G. Can. J. Chem. 1984, 62, 798.
25. Grossert, J. S.; Dubey, P. K.; Elwood, J. Can. J. Chem.
1985, 63, 1263.
26. Stewant, S. K.;Whiting, A. TetrahedronLett. 1995, 36, 3929.
27. (a) Dickerson, T. J.; Reed, N. N.; Janda, K. D. Chem. Rev.
2002, 102, 3325; (b) Kamal, A.; Reddy, D. R.; Rajender
Tetrahedron Lett. 2005, 46, 7951.
18. Trost, B. M. Chem. Rev. 1978, 78, 363.
19. Ramaiah, K.; Dubey, P. K.; Ramanandham, J. Indian
J. Chem. 1999, 38, 297.