Synthesis of B-Ketosulfones Promoted by Sulfonylbenzenes

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Synthesis of B-Ketosulfones Promoted by Sulfonylbenzenes

K. Ashalatha

Kommuri Pratap Reddy Institute of Technology

AbstractAn efficient and convenient synthesis of -ketosulfones is described. Reaction of sulfonylbenzene with haloketone yields the corresponding -ketosulfone promoted by as an efficient reaction medium.

Among sulfur containing compounds, -ketosulfones are an important group of intermediates1 in Michael and Knoevenagel reactions,2,3 and are valuable precursors in the synthesis of acetylenes, allenes, chalcones,49vinylsulfones10and polyfunctionalized 4H-pyrans.11-Ketosulfones are useful for the synthesis of ketones by facile reductive elimination of the sulfone group12and also in the preparation of epoxy sulfones.13In addition, -ketosulfones are precursors for optically active -hydoxysulfones.14 Although several methods for their synthesis1524 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 -ketosulfones.

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 and their inexpensive and eco-friendly nature. In this connection, we report a synthesis of – ketosulfones in the presence of PEG-400 as an efficient reaction medium.

Reaction of sulfonylbenzene with a phenacyl bromide/phenacyl chloride in reuxing ethanol for 1012 h resulted in the formation of the corresponding -ketosulfone in 50% yield. However, when we carried out the reaction, the formation – ketosulfone 3(Scheme1), was complete in 5min in 96% yield. Encouraged by the speed of the reaction, various -haloketones were reacted with sulphonylbenzene in PEG-400 to yield

-ketosulphones3 in excellent yields. The reaction is facile even with hindered -haloketones, such as those in entries 13 and 17 in Table2. In order to compare the rate of the reaction in PEG-400, we carried out the reaction in different solvents(Table1).

Keywords: Polyethylene glycol (PEG-400); -ketosulfones; – haloketone; sulfonylbenzene.

Table 1. Solvent efficient on the reaction of phenacyl bromide with sulfonylbenzene at room temperature

Entry

Solvent

Time

Yield (%)

1

PEG

10 min

96

2

PEG/CH3CN (1:1)

10 min

95

3

EtOH

24 h

50

4

CH3CN

24 h

49

5

IPA

24 h

40

6

C6H6

24 h

Nil

7

CHCl3

24 h

Nil

8

DCM

24 h

Nil

The poor 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 PhSO2 is solvated in

hðydroxylicÞ 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, Table2).

In conclusion, we have disclosed an inexpensive, fast and efficient synthesis of -ketosulfones using polyethylene glycol 400 as the reaction medium.

Typical experimental procedure (Scheme 1): A mixture of the sulfonylbenzene (1.1 mmol) and the – haloketones (1mmol) was taken in 10ml of polyethylene glycol, and stirred at room temperature for the appropriate time(see Table2). 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 puried by column chromatography or crystallized from methanol. The PEG was recovered from the aqueous layer and reused without loss of activity.

Table 2. Synthesis of -ketosulfones by using polyethylene glycol (PEG-400) as an efficient reaction medium at room temperature Entry -Haloketones Sulfonylbenzene Product Time(min) Yielda(%)

O

  1. Br

    SO2H

    O O

    S 10 96

    O

    O

  2. Br

    O

    SO2H

    CH3

    O O

    S

    O

    CH3

    O O

    10 95

    3

    3

  3. Br CH3SO2H S CH

30 80

O

O SO H O O

2

Br

4

H3C

S

O

H3C

10 95

5

H3C

O SO2H

Br

CH3

O SO2H

O O

S

O

H3C CH3

O O

10 90

  1. Br

    HO

    O

  2. Br

    HO

    O

  3. Br

    Cl

    SO2H

    CH3 SO2H

    S

    10 95

    O

    HO

    O O

    S

    10 93

    O

    HO CH3

    O O

    S

    CH3

    O

    Cl CH3

    10 93

    Table 2 (continued)‌‌‌

    Entry -Haloketones Sulfonylbenzene Product Time(min) Yielda(%)

    O

  4. Br

Cl

O

Br

SO2H

SO2H

O O

S 10 94

O

Cl

O O

S

10 O 10 95

O SO2H

Br

11

CH3

O

Br

  1. CH3SO2H

    SO2H

    O

    O O

    S O

    O O

    S

    CH3

    O

    O O

    CH3

    10 90

    10 92

  2. Br

CH3

O

14 Br

H3C

O

CH3 SO2H

SO2H

S

O

CH3 CH3

O O

S

H3C

O

O O

S

10 90

10 95

  1. Br

    H3C

    O

    CH3

    H3C

    O

    O OSC

    CH3

    10 95

  2. Br CH3SO2H HC

    H 10 95

    H3C

    O

    3 3

    O

    O

    O

    SO2H

    O

  3. Br

CN

CH

S

O

CN CH3

30 90

3

aIsolated yields after column chromatography/crystallization and all products gave satisfactory spectral and analytical data.

REFERENCES AND NOTES

  1. Simpkins,N.S.InSulfonesinOrganicSynthesis;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.ActaChim.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.; Lade,

    T. G. Tetrahedron Lett. 1995, 36,7925.

  6. Reddy,M.V.R.;Reddy,S.ActaChim.Hung.1985,120,275.

[7] Looker, J. J. J. Org. Chem. 1966, 31, 2714.

  1. Sengupta,S.;Sarma,D.S.;Mondal,S.Tetrahedron1998,54, 9791.

  2. Sengupta, S.; Sarma, D. S.; Mondal, S. Tetrahedron: Asymmetry

    2001, 12,513.

  3. Sengupta, S.; Sarma, D. S.; Mondal, S. Tetrahedron: Asymmetry

    1998, 9,2311.

  4. (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.

  5. (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.rg.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.

  6. Trost, B. M. In Comprehensive Organic Chemistry;Perg- amon Press, 1993; Vol. 1, p 530.

  7. (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.; Phansavath, P.; Vidal, V. R.; Genet, J. P.; Touati, A. R.; Homri,T.;Hassine,B.B.Tetrahedron:Asymmetry1999,10,1369; (c) Gotor, V.; Rebolledo, F.; Liz, R. Tetrahedron: Asym- metry 2001, 12, 513.

  8. (a) Schank, K.; Weber, A. Synthesis 1970, 367; (b) Schank, K.

    Annalen 1967, 75, 702.

  9. Julia, M.; Paris, J. M. Tetrahedron Lett. 1973, 14,4833.

  10. Durst,T.In ComprehensiveOrganicChemistry;Barton,D. H. R., Ollis, W. D., Eds.; Peragmon Press: Oxford, UK, 1979; Vol. 4, Chapter 11.8, p 174. 18.

[18] Trost, B. M. Chem. Rev. 1978, 78, 363.

  1. Ramaiah, K.; Dubey, P. K.; Ramanandham, J. Indian J. Chem.

    1999, 38,297.

  2. Holmquist, C. R.; Roskamp, E. J. Tetrahedron Lett.1992, 33, 1131.

  3. Kamigata, N.; Udodaira, K.; Shimizu, T. J. Chem. Soc., Perkin Trans. 1. 1997,783.

  4. Field, L.; Lawson, J. E.; Mc Fenland, J. W. J. Am. Chem. Soc.

    1956, 78,4389.

  5. Kartrizky, A. R.; Ashraf, A. A.; Fattah, A.;Mingyiwang J. Org. Chem. 2003, 68, 1443.

  6. Grossert, J. S.; Dubey, P. K.; Gill, G. H.; Stancey, T.; Cameron,S.T.;Patric,A.G.Can.J.Chem.1984,62,798.

  7. Grossert,J.S.;Dubey,P.K.;Elwood,J.Can.J.Chem.1985, 63, 1263.

  8. Stewant,S.K.;Whiting,A.TetrahedronLett.1995,36,3929.

  9. (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.

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