4-Bromobenzenesulfonyl Chloride

[98-58-8]  · C6H4BrClO2S  · 4-Bromobenzenesulfonyl Chloride  · (MW 225.52)

(N-protection of amines; formation of sulfonamides, sulfonate esters, and carbodiimides)

Alternate Name: BsCl.

Physical Data: mp 73-75 °C.

Solubility: sol Et2O, THF, petroleum ether and 1,4-dioxane.

Preparative Method: reaction of sodium p-bromobenzenesulfonate with Phosphorus(V) Chloride gives a 90% yield.1

Handling, Storage, and Precautions: harmful by skin absorption and ingestion and causes burns. The reagent is moisture sensitive and will react with nucleophilic solvents, e.g. alcohols, liberating HCl and therefore should be stored under an inert atmosphere.

Protection of Nitrogen, Formation of Sulfonamides.

p-Bromobenzenesulfonyl chloride (BsCl) has been widely used to N-protect amines (eqs 1 and 2)2,3 (see also p-Toluenesulfonyl Chloride and Benzenesulfonyl Chloride). Due to the relatively high molecular weight, p-bromobenzenesulfonyl derivatives have a higher melting point and may be more readily crystallizable than lower molecular weight derivatives.

The electron-withdrawing nature of the p-bromobenzenesulfonyl group has been used, via the sulfonamide derivative of a pyridone, in inverse electron demand Diels-Alder reactions to great effect.4

Disulfonamides can be prepared from primary amines (eq 3), thereby converting the amine into a better leaving group.5 The syntheses of sulfonamides derived from sulfamates have also been reported.6

Formation of Sulfonate Esters.

The reaction of hydroxy groups with p-bromobenzenesulfonyl chloride gives p-bromobenzenesulfonates (brosylates) (eq 4).7 The brosylate ester transforms the hydroxy functional group into a good leaving group and this has been exploited in synthesis. Inositol derivatives8 have been prepared using brosylates in preference to the corresponding 4-methylbenzenesulfonates, the latter being a less effective leaving group in this particular case.

The reaction of b-hydroxy acids with p-bromobenzenesulfonyl chloride in the presence of a tertiary amine gives b-lactones (eq 5).9,10 Brosylate esters of oximes have been manipulated in the Beckmann rearrangement of erythromycin derivatives11 as an alternative to both 4-methylbenzenesulfonate esters and benzenesulfonate esters.

Formation of Carbodiimides.

p-Bromobenzenesulfonyl chloride reacts with ureas to form carbodiimides in good yield (eq 6).12

Reaction with Alkenes and Arenes.

p-Bromobenzenesulfonyl chloride will undergo desulfonylative coupling to alkenes and arenes using PdII catalysis (eq 7).13

1. Marvel, C. S.; Smith, F. E. JACS 1923, 45, 2696.
2. Pavlidis, V. H.; Chan, E. D.; Pennington, L.; McParland, M.; Whitehead, M.; Coutts, I. G. C. SC 1988, 18, 1615.
3. Hamanaka, N.; Seko, T.; Miyazuki, T.; Naka, M.; Furuta, K.; Yamamoto, H. TL 1989, 30, 2399.
4. Posner, G. H.; Switzer, C. JOC 1987, 52, 1642.
5. (a) DeChristopher, P. J.; Adamek, J. P.; Lyon, G. D.; Klein S. A.; Baumgarten, R. J. JOC 1974, 39, 3525. (b) DeChristopher, P. J.; Adamek, J. P.; Sanford, A. K.; Lyon, G. D.; Baumgarten, R. J. JOC 1975, 40, 3288.
6. Spillane, W. J.; Burke, P. O. S 1986, 1021.
7. Shiner, V. J.; Ensinger, M. W.; Huffmann, J. C. JACS 1989, 111, 7199.
8. Espelie, K. E.; Anderson, L. Carbohydr. Res. 1976, 46, 53.
9. Pu, Y.; Martin, F. M.; Vederas, J. C. JOC 1991, 56, 1280.
10. Pansare, S. V.; Vederas, J. C. JOC 1989, 54, 2311.
11. Djokic, S.; Kobrehel, G.; Lazarevski, G.; Lopotar, N.; Tamburasev, Z.; Kamenar, B.; Nagl, A.; Vickovic, I. JCS(P1) 1986, 1881.
12. Jaszay, Z. M.; Petnehazy, I.; Toke, L.; Szajani, B. S 1987, 520.
13. Miura, M.; Hashimoto, H.; Itoh, K.; Nomura, M. JCS(P1) 1990, 2207.

Hayley Binch & Stephen Thompson

University of Bristol, UK

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