Benzenesulfinyl Chloride1

(1; R = Ph)

[4972-29-6]  · C6H5ClOS  · Benzenesulfinyl Chloride  · (MW 160.62) (2; R = p-Tol)

[10439-23-3]  · C7H7ClOS  · p-Toluenesulfinyl Chloride  · (MW 173.64) (±)-(2)


(preparation of sulfoxides2 and sulfones;3 synthesis of chiral sulfinyl-transfer reagents4,5)

Physical Data: (1) mp 38 °C, bp 71-72 °C/1.5 mmHg; d25 1.3470 g cm-3, n25D 1.5770; (2) mp 54-58 °C, bp 113-115 °C/3.5 mmHg; n23.5D 1.6004.

Solubility: sol Et2O, CHCl3; decomposes in H2O and alcohol.

Analysis of Reagent Purity: 1H NMR,6b IR.6c

Preparative Methods: reaction of Sodium Benzenesulfinate or sodium p-toluenesulfinate with Thionyl Chloride.6a

Handling, Storage, and Precautions: it has been reported that arenesulfinyl chlorides should not be distilled above 2 mmHg pressure because of the danger of explosion.6d Care also should be taken to avoid exposure of these sulfinyl chlorides to moisture (i.e. air, skin) owing to decomposition and formation of corrosive HCl.

Preparation of Sulfinyl Compounds.

Arenesulfinyl chlorides react with carbon nucleophiles such as enolates and Grignard reagents to produce sulfinylated compounds capable of undergoing further useful transformations;2 sulfinyl esters react similarly (see Methyl Benzenesulfinate). Incorporation of the sulfinyl group has been used for the regioselective alkylation of ketones via their dianions;7 the sulfinyl group can be removed reductively with Al(Hg) (eq 1),8 or eliminated with concomitant formation of a double bond to form a,b-unsaturated ketones (eq 2).9 This process is one of the better methods of introducing a double bond into a molecule; this procedure also has found use as an alternative when the popular phenylselenylation-oxidation method was deemed unsuccessful.10

Preparation of Unsaturated Sulfoxides and Sulfones.2,11,12

Alkenes can be converted directly to allylic sulfoxides with p-toluenesulfinyl chloride in the presence of Ethylaluminum Dichloride13 or Zinc Chloride14 via an ene reaction. Treatment of the allylic sulfoxides with trimethyl phosphite in methanol affords the allylic alcohols via sulfoxide-sulfenate rearrangement in higher yields compared to direct oxidation with Selenium(IV) Oxide (eq 3).14 Sulfinylation of higher terpenoids with benzenesulfinyl chloride was found to be more regioselective than the procedure of sulfenylation with benzenesulfenyl chloride followed by oxidation.14

Allylic sulfinic esters, prepared by reaction of p-toluenesulfinyl chloride and an allylic alcohol, rearrange on heating to yield allylic sulfones;15 sulfinic esters of alkynols rearrange to yield sulfonylallenes (eq 4).16

Asymmetric Synthesis.

p-Toluenesulfinyl chloride can be used to prepare menthyl p-toluenesulfinates (MenTs) (see (-)-(1R,2S,5R)-Menthyl (S)-p-Toluenesulfinate), very useful chiral sulfinyl-transfer reagents.4 Both the (R) and the (S) isomers can be prepared by reaction of the sulfinyl chloride with either (+)- or (-)-menthol, respectively.17,18 (See Methyl Benzenesulfinate for additional discussion on menthyl p-toluenesulfinate.) MenTs reacts with a variety of nucleophiles such as metallated esters,19 dialkylhydrazones,20 and amides,21 with inversion of configuration, to form chiral sulfoxides. These substrates are capable of undergoing further enantioselective manipulation to yield optically active compounds in high enantiomeric excess.22,23

Chiral vinyl sulfoxides can be prepared from MenTs and metallated vinylic reagents;24 vinyl sulfoxides are recognized as valuable synthetic intermediates.11 For example, the conjugate addition of organometallic compounds to enantiomerically pure 2-(p-tolylsulfinyl)-2-cyclopentenones occurs with high stereoselectivity; the formation of the desired stereoisomer can be controlled by the presence or absence of a divalent metal complexing agent (eq 5).24

Other routes to chiral vinyl sulfoxides utilizing MenTs include a modified Horner-Emmons procedure that usually results in a mixture of (E) and (Z) isomers (eq 6),17 and addition of alkynyl Grignard reagents to MenTs followed by stereospecific reduction to either the (E) or (Z) isomers (eq 7).25

Recently, a new class of chiral sulfinylating agents have been prepared from oxazolidinones and p-toluenesulfinyl chloride (eq 8).5 These N-sulfinyloxazolidinones also react with a wide range of nucleophiles, with inversion of configuration, to form chiral sulfoxides in high yield and enantiomeric excess (ee). These reagents reportedly are purified more easily (crystallization and chromatography) than the menthyl esters (crystallization only), and are more reactive than the menthyl p-toluenesulfinates.

1. Tillett, J. G. The Chemistry of Sulphinic Acids, Esters, and Their Derivatives; Patai, S., Ed.; Wiley: Chichester, 1990; pp 577-602.
2. (a) Drabowicz, J.; Kielbasinski, P.; Mikolajczyk, M. The Chemistry of Sulphones and Sulphoxides; Patai, S.; Rappoport, Z.; Stirling, C., Eds.; Wiley: Chichester, 1988; pp 233-378. (b) Field, L. S 1978, 713; S 1972, 101.
3. Schank, K. The Chemistry of Sulphones and Sulphoxides; Patai, S.; Rappoport, Z.; Stirling, C., Eds.; Wiley: Chichester, 1988; pp 165-232.
4. Solladie, G. S 1981, 185.
5. Evans, D. A.; Faul, M. M.; Colombo, L.; Bisaha, J. J.; Clardy, J.; Cherry, D. JACS 1992, 114, 5977.
6. (a) Kurzer, F. OSC 1963, 4, 937. (b) Youn, J-H.; Herrmann, R. S 1987, 72. (c) Tanaka, Y.; Sugimura, T.; Tanaka, Y. CPB 1965, 13, 1384. (d) Kee, M.-L.; Douglass, I. B. OPP 1970, 2, 235.
7. Kuwajima, I; Iwasawa, H. TL 1974, 107.
8. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. TL 1987, 28, 4629.
9. Roush, W. R.; Walts, A. E. JACS 1984, 106, 721.
10. Magnus, P.; Pappalardo, P. JACS 1983, 105, 6525.
11. De Lucchi, O.; Pasquato, L. T 1988, 44, 6755.
12. Posner, G. H. The Chemistry of Sulphones and Sulphoxides; Patai, S.; Rappoport, Z.; Stirling, C., Eds.; Wiley: Chichester, 1988; pp 823-850.
13. Snider, B. B. JOC 1981, 46, 3155.
14. Moiseenkov, A. M.; Dragan, V. A.; Koptenkova, V. A.; Veselovsky, V. V. S 1987, 814.
15. Knight, D. J.; Whitham, G. H.; Williams, J. G. JCS(P1) 1987, 2149.
16. Ohmori, M.; Takano, Y.; Yamada, S.; Takayama, H. TL 1986, 27, 71.
17. Solladie, G.; Moine, G. JACS 1984, 106, 6097.
18. Solladie, G.; Hutt, J.; Girardin, A. S 1987, 173.
19. Papageorgiou, C.; Benezra, C. TL 1984, 25, 1303.
20. Banfi, L.; Colombo, L.; Gennari, C. S 1982, 829.
21. Annunziata, R.; Cinquini, M.; Cozzi, F.; Montanari, F.; Restelli, A. T 1984, 40, 3815.
22. Walker, A. J. TA 1992, 3, 961.
23. Solladié, G. PAC 1988, 60, 1699.
24. (a) Hulce, M.; Mallamo, J. P.; Frye, L. L.; Kogan, T. P.; Posner, G. H. OS 1986, 64, 196. (b) Posner, G. H. ACR 1987, 20, 72.
25. Kosugi, H.; Kitaoka, M.; Tagami, K.; Takahashi, A.; Uda, H. JOC 1987, 52, 1078.

Jeffrey D. Macke

Miles Inc., Kansas City, MO, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.