p-Toluenesulfinic Acid

[536-57-2]  · C7H8O2S  · p-Toluenesulfinic Acid  · (MW 156.22) (Na salt.H2O)

[824-79-3]  · C7H9O3NaS  · p-Toluenesulfinic Acid  · (MW 196.22)

(preparation of alkyl, vinyl, and allyl sulfones; starting material for the preparation of chiral sulfoxides; mild acid catalyst)

Physical Data: mp 85 °C; pKa 1.66. The sodium salt hydrate has mp >300 °C.1

Solubility: sol ethanol, ether; sparingly sol water, hot benzene.

Form Supplied in: commercially available as the sodium salt hydrate; the lithium salt [16844-27-2] is also available.

Preparative Methods: isolation of the free acid via acidification of an aqueous solution of the sodium salt has been described;1b partial conversion to p-Toluenesulfonic Acid frequently accompanies drying of the free acid.

Purification: recrystallizes in water in long rhombic needles or plates.

Handling, Storage, and Precautions: should be stored in a cool, dry place away from strong oxidizing agents.

Synthesis of Sulfones.

p-Toluenesulfinic acid is a frequently used reagent for the synthesis of organic sulfones. The sulfone group has played an extensive role in recent synthetic organic chemistry; some of its common applications are described below, following preparation of representative sulfones from the title reagent. Unless otherwise noted, the reactions described use the sodium salt rather than the free acid.

Alkylation of arenesulfinate salts is a very general reaction for the preparation of alkyl sulfones.2 Reaction conditions utilizing alcoholic or dipolar aprotic solvents are typical, but phase-transfer conditions have been described.3 Reaction with reactive halides is generally facile (eq 1);4 triflates have likewise been displaced with ease by p-toluenesulfinate.5

The sulfones so obtained are useful in a variety of organic transformations. Alkyl sulfones are readily deprotonated with bases, and the resulting carbanions are good nucleophiles. Sulfones thus function as activating groups which can subsequently be removed under mild conditions.6 Alkylation of alkyl sulfones by alkyl halides, followed by reductive cleavage with Lithium metal or Sodium Amalgam, provides a method of coupling alkyl halides which has been useful in the synthesis of 1,4-dienes.7 Sodium p-toluenesulfinate also undergoes conjugate addition reactions8 and has been used as a nucleophile in palladium-catalyzed substitution reactions of allylic substrates.9

The addition of sulfone-substituted anions to carbonyl compounds yields b-hydroxy sulfones. These are useful intermediates for the synthesis of unsaturated compounds via elimination processes.10-13 b-Hydroxy sulfones may also be prepared via the regioselective ring opening of epoxides by sodium p-toluenesulfinate.14

The radical addition of sulfinates to unsaturated compounds via the iodosulfonylation-dehydroiodination15 reaction sequence constitutes a general method for the preparation of vinyl sulfones; the latter may be rearranged to allylic sulfones by treatment with base.16 The radical addition may be carried out on a,b-unsaturated carbonyl compounds as well as alkenes.17 In the case of unsaturated carbonyl compounds the elimination process can be quite stereoselective, (E)-alkenes being normally formed. For the addition to nonconjugated alkenes, conditions have been described for the preparation of either (E)- or (Z)-alkenes.16

Cleavage of Vinylsilanes.

p-Toluenesulfinic acid has been used for the protodesilylation of vinylsilanes to provide alkenes.18 This method is milder than the usual strong acids used for this purpose. The cleavage is not stereospecific.

Synthesis of Chiral Sulfoxides.

Chiral sulfoxides have been used extensively in asymmetric synthesis.19 An extremely common method for the preparation of these compounds involves the reaction of resolved diastereomeric sulfinate esters with Grignard reagents and organolithium species.20 Menthol has classically been used to form diastereomeric esters of p-toluenesulfinic acid; an improved method using sulfinate esters of trans-2-phenylcyclohexanol has recently been reported.21

1. (a) Dictionary of Organic Compounds, 5th ed., Third Supplement; Chapman and Hall: New York, 1985; p 292. (b) The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 11th ed.; Budavari, S., Ed.; Merck: Rahway, NJ, 1989; p 1501.
2. Meek, J. S.; Fowler, J. S. JOC 1968, 33, 3422.
3. Crandall, J. K.; Pradat, C. JOC 1985, 50, 1327.
4. Cox, C. M.; Whiting, D. A. JCS(P1) 1991, 1901.
5. Tanner, D.; Somfai, P. T 1987, 43, 4395.
6. For reviews, see (a) Durst, T. In Comprehensive Organic Chemistry; Barton, D. H. R.; Ollis, W. D., Eds.; Pergamon: Oxford, 1979; Vol. 3, p 171. (b) Magnus, P. D. T 1977, 33, 2019.
7. Grieco, P. A.; Masaki, Y. JOC 1974, 39, 2135.
8. Sánchez, I. H.; Aguilar, M. A. S 1981, 55.
9. Safi, M.; Sinou, D. TL 1991, 32, 2025.
10. Julia, M.; Paris, J. M. TL 1973, 4833.
11. Otera, J.; Misawa, H.; Sugimoto, K. JOC 1986, 51, 3830.
12. Kocienski, P. J.; Lythogue, B.; Ruston, S. J. JCS(P1) 1978, 829.
13. Achmatowicz, B.; Baranowska, E.; Daniewski, A. R.; Pankowski, J.; Wicha, J. T 1988, 44, 4989.
14. Biswas, G. K.; Bhattacharyya, P. SC 1991, 569.
15. Barluenga, J.; Martinez-Gallo, J. M.; Nájera, C.; Fañanás, F. J.; Yus, M. JCS(P1) 1987, 2605.
16. Kobayashi, T.; Tanaka, Y.; Ohtani, T.; Kinoshita, H.; Inomata, K.; Kotake, H. CL 1987, 1209.
17. Nájera, C.; Baldó, B.; Yus, M. JCS(P1) 1988, 1029.
18. Büchi, G.; Wüest, H. TL 1977, 4305.
19. (a) Solladié, G. S 1981, 185. (b) Posner, G. H. ACR 1987, 20, 72.
20. (a) Solladié, G.; Hutt, J.; Girardin, A. S 1987, 173. (b) Hulce, M.; Mallamo, J. P.; Frye, L. L.; Kogan, T. P.; Posner, G. H. OS 1986, 64, 196; OSC 1990, 7, 495.
21. Whitesell, J. K.; Wong, M.-S. JOC 1991, 56, 4552.

Gregory S. Hamilton

Scios Nova, Baltimore, MD, USA

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