Benzenesulfonyl Chloride

[98-09-9]  · C6H5ClO2S  · Benzenesulfonyl Chloride  · (MW 176.62)

(used in a range of sulfonating reactions to produce sulfonamides,5-7 sulfonate esters,8-10 mixed anhydrides,13 and sulfones 15-17)

Physical Data: mp 13-15 °C, bp 251.5 °C/760 mmHg, 113-115 °C/10 mmHg; d 1.384 g cm-3.

Solubility: sol CH2Cl2, Et2O, THF, C6H6, MeCN.

Preparative Methods: prepared by reaction of sodium benzenesulfonate with phosphorus pentachloride or phosphorus oxychloride,1 or by chlorosulfonation of benzene;2 also commercially available.

Purification: may be purified by distillation at reduced pressure.

Handling, Storage, and Precautions: benzenesulfonyl chloride is an irritant and harmful by skin absorption and ingestion. 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. Use in a fume hood.

Identification of Primary Amines; the Hinsberg Test.

Benzenesulfonyl chloride is used to recognize primary amines. A primary amine will react to form an alkali-soluble benzenesulfonamide (containing an acidic NH), whereas secondary amines form sulfonamides which are insoluble in alkali, and tertiary amines do not react.3 However, the validity of the test is dependent on reaction velocity, concentration, temperature, and solubility4 and appropriate precautions must be acknowledged.

Protection of Nitrogen; Formation of Sulfonamides.

Benzenesulfonyl chloride is used to protect amines, indoles and other nitrogen based functional groups (eqs 1-3).5-7 A variety of bases and solvents can be used, depending on the substrate. Other arene- and alkanesulfonyl chlorides can also be used for this purpose (see p-Toluenesulfonyl Chloride and Methanesulfonyl Chloride). Sulfonamide cleavage may be achieved under either acidic or basic conditions.

Formation of Sulfonate Esters.

The reaction of phenols,8 alcohols,9 and N-hydroxy compounds10 with benzenesulfonyl chloride produces O-sulfonate esters, one application of which is as a good leaving group.

The reaction of 1,4- or 1,5-diols with benzenesulfonyl chloride in the presence of a tertiary amine gives cyclic ethers (eq 4).11 This procedure can be adapted to give cyclic tertiary amines.12

Formation of Mixed Anhydrides.

Benzenesulfonyl chloride will react with carboxylic acids to give mixed anhydrides,13 which can be utilized in the formation of alkenes via b-lactone formation followed by fragmentation (eq 5).14 Direct conversion of the hydroxy acid to the alkene can be achieved by the addition of benzenesulfonyl chloride at 45-50 °C in 55-82% yield.

Addition to Unsaturated Compounds.

Benzenesulfonyl chloride will undergo radical addition to alkenes and alkynes under radical conditions (eq 6)15 or CuII catalysis (eq 7).16

Addition of benzenesulfonyl chloride to trimethylsilyl enol ethers gives b-keto sulfones in good yield (eq 8).17

Reaction with Arenes.

Benzenesulfonyl chloride will react with arenes in the presence of Aluminum Chloride to give biaryl sulfones.18

1. Adams, R.; Marvel, C. S. OSC 1941, 1, 84.
2. Clarke, H. T.; Babcock, G. S.; Murray, T. F. OSC 1941, 1, 85.
3. Coleman, G. H.; Nichols, G.; Marten, T. F. OSC 1955, 3, 159.
4. Gambill, C. R.; Roberts, T. D. J. Chem. Educ. 1972, 49, 287.
5. Gribble, G. W.; Saulnier, M. G.; Sibi, M. P.; Obaza-Nutaitis, J. A. JOC 1984, 49, 4518
6. Buckley, T. F.; Rapoport, H. JACS 1981, 103, 6157.
7. Gordon, M. S.; Krause, J. G.; Linnemanmohr, M. A.; Parchue, R. P. S 1980, 244.
8. (a) Bazile, Y.; De Cointet, P.; Pigerol, C. JHC 1978, 15, 859. (b) Shah, J. J. J. Pharm. Sci. 1977, 66, 440.
9. Herzog, H. L. OSC 1963, 4, 753.
10. (a) Van Verst, M. E.; Bell, C. L.; Bauer, L. JHC 1979, 16, 1329. (b) Itoh, M.; Nojima, H.; Notani, J.; Hagiwara, D.; Takai, K. BCJ 1978, 51, 3320.
11. Reynolds, D. D.; Kenyon, W. O. JACS 1950, 72, 1593.
12. Reynolds, D. D.; Kenyon, W. O. JACS 1950, 72, 1597.
13. Urbanski, J.; Manek, M. B. Pol. J. Chem. 1984, 58, 1227.
14. Adam, W.; Baeza, J.; Lui, J. C. JACS 1972, 94, 2000.
15. Vasil'eva, M. A.; Bychkova, T. I.; Kushnarev, D. F.; Rozova, T. I.; Kalabina, A. V. ZOR 1977, 13, 283.
16. Asscher, M.; Vofsi, D. JCS 1964, 4962.
17. Yoshiaki, K.; Muria, S.; Sonoda, N.; Tsutsumi, S. Organomet. Chem. Synth. 1972, 1, 465.
18. Jensen, F. R.; Brown, H. C. JACS 1958, 80, 4038.

Hayley Binch

University of Bristol, UK

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