o-Nitrobenzenesulfenyl Chloride1

[7669-54-7]  · C6H4ClNO2S  · o-Nitrobenzenesulfenyl Chloride  · (MW 189.63)

(protection of amino groups1d,2 and thiols;3 sulfenylation of alkenes;4 preparation of sulfoxides from alcohols5)

Alternate Name: NPS-Cl.

Physical Data: mp 74-76 °C.

Preparative Methods: by addition of Chlorine to (o-O2NC6H4S)2.6

Form Supplied in: yellow solid; widely available.

Handling, Storage, and Precautions: corrosive and moisture sensitive; decomposes within a few days when exposed to moist air, with liberation of HCl.

Protection of Amines.

Reaction of amines with o-O2NC6H4SCl in the presence of a base produces the corresponding sulfenamide (eq 1). Such 2-nitrophenylsulfenyl (NPS)-protected amines have been used primarily in peptide chemistry.2 They have also seen service in the synthesis of cephalosporins,7 nucleosides,8 and N-acyl b-lactones.9 The NPS group is cleaved by acid hydrolysis (e.g. HOAc or HCl),2 by nucleophiles (e.g. HSCH2CH2OH, HSCH2COOH, 2-mercaptopyridine,10 NaI,7 thioacetamide,11 Bu3P8,12), or with Raney nickel.13 Other arylsulfenyl chlorides have been used for amine protection, but those with ortho-nitro groups provide the most stable derivatives.1d N-NPS-saccharin has been proposed as a more stable substitute for NPS-Cl.14

Protection of Thiols.

Mercapto groups (e.g. on cysteine) may be protected as mixed disulfides using NPS-Cl (eq 2).3 The free thiol may be regenerated by reduction (NaBH4) or by treatment with other thiols (e.g. HSCH2CO2H, HSCH2CH2OH). Treatment of t-butyl thiols with NPS-Cl followed by reduction constitutes a useful method for the removal of the t-butyl group.3c,3d Sulfenates of sugar derivatives have been prepared but sulfenates have not been widely used as hydroxyl protecting groups in synthesis.15

Sulfenylation of Alkenes.

Treatment of alkenes bearing suitably disposed nucleophilic functionalities with sulfenyl chlorides gives rise to cyclic products (eq 3). Benzenesulfenyl Chloride has been used most commonly in this capacity,1a-c but NPS-Cl has also been employed.4

Preparation of Sulfoxides from Alcohols.

Allylic and propargylic alcohols react with sulfenyl chlorides to produce intermediate sulfenates which undergo a [2,3]-sigmatropic rearrangement to allylic and allenic sulfoxides, respectively (eq 4).5 There has been considerable interest in the mechanism, stereochemistry, and synthetic applications of this reaction.5,16 Many sulfenyl chlorides have been used, including NPS-Cl.17

1. (a) Capozzi, G.; Modena, G.; Pasquato, L. In The Chemistry of Sulphenic Acids and their Derivatives; Patai, S., Ed.; Wiley: Chichester, 1990; Chapter 10. (b) Kühle, E. S 1971, 563. (c) Kühle, E. S 1971, 617. (d) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991; pp 377-379. (e) Craine, L.; Raban, M. CRV 1989, 89, 689.
2. (a) Zervas, L.; Borovas, D.; Gazis, E. JACS 1963, 85, 3660. (b) Zervas, L.; Hamalidis, C. JACS 1965, 87, 99. (c) Kricheldorf, H. R.; Fehrle, M. S 1974, 422.
3. (a) Fontana, A. CC 1975, 976. (b) Fontana, A.; Scoffone, E.; Benassi, C. A. B 1968, 7, 980. (c) Pastuszak, J. J.; Chimiak, A. JOC 1981, 46, 1868. (d) Divakar, K. J.; Mottoh, A.; Reese, C. B.; Sanghvi, Y. S. JCS(P1) 1990, 969.
4. Zefirov, N. S.; Koz'min, A. S.; Kirin, V. N.; Zhdankin, V. V.; Caple, R. JOC 1981, 46, 5264.
5. Braverman, S. In The Chemistry of Sulphenic Acids and their Derivatives; Patai, S., Ed.; Wiley: Chichester, 1990; Chapter 8.
6. Hubacher, M. H. OSC 1943, 2, 455.
7. (a) Kobayashi, T.; Iino, K.; Hiraoka, T. JACS 1977, 99, 5505. (b) Gordon, E. M.; Cimarusti, C. M. TL 1977, 1359. (c) Welch, W. M. JOC 1976, 41, 2220.
8. (a) Heikkilä, J.; Balgobin, N.; Chattopadhyaya, J. ACS(B) 1983, 37, 857. (b) de Vroom, E.; Spierenburg, M. L.; Dreef, C. E.; van der Marel, G. A.; van Boom, J. H. RTC 1987, 106, 65.
9. (a) Rao, M. N.; Holkar, A. G.; Ayyangar, N. R. CC 1991, 1007. (b) Lowe, C.; Pu, Y.; Vederas, J. C. JOC 1992, 57, 10.
10. Tun-Kyi, A. HCA 1978, 61, 1086.
11. Chimiak, A.; Pastuszak, J. J. CI(L) 1971, 427.
12. Kuyl-Yeheskiely, E.; Tromp, C. M.; Lefeber, A. W. M.; van der Marel, G. A.; van Boom, J. H. T 1988, 44, 6515.
13. Meienhofer, J. Nature 1965, 205, 73.
14. Romani, S.; Bovermann, G.; Moroder, L.; Wünsch, E. S 1985, 512.
15. Fokt, I.; Szeja, W. Carbohydr. Res. 1991, 222, 271.
16. Evans, D. A.; Andrews, G. C. ACR 1974, 7, 147.
17. (a) Padwa, A.; Bullock, W. H.; Norman, B. H.; Perumattan, J. JOC 1991, 56, 4252. (b) Padwa, A.; Gareau, Y.; Harrison, B.; Norman, B. H. JOC 1991, 56, 2713. (c) Altenbach, H.-J.; Soicke, H. LA 1982, 1096.

J. Michael Chong

University of Waterloo, Ontario, Canada

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