Mesitylenesulfonyl Chloride

[773-64-8]  · C9H11ClO2S  · Mesitylenesulfonyl Chloride  · (MW 218.72)

(preparation of sulfonates;1 condensing agent in nucleotide synthesis2)

Alternate Name: 2,4,6-trimethylbenzenesulfonyl chloride.

Physical Data: mp 55-57 °C.

Solubility: sol organic solvents.

Form Supplied in: white crystalline solid; widely available.

Purification: can be recrystallized from hexane or pentane.

Handling, Storage, and Precautions: corrosive; moisture sensitive; handle and store under nitrogen.

Sulfonamide Formation.

Reaction of mesitylenesulfonyl chloride with amines in the presence of Pyridine or Triethylamine yields the corresponding sulfonamides (eq 1),3 which have been used as intermediates in synthesis.

The mesityl group has been used as a protecting group for various amines including amino acids (eq 2)4 and peptides.5-7

The mesitylsulfonyl-protected amino acids can be deblocked by treatment with Hydrogen Bromide and Acetic Acid. The stability of the sulfonamide towards both acidic and basic conditions makes it a useful protecting group for peptide synthesis. The mesitylenesulfonyl group has been used to protect the indole group of tryptophan6 and the guanidine group of arginine.7 These mesityl derivatives can be cleaved with Trifluoromethanesulfonic Acid or Methanesulfonic Acid. Partial cleavage of the guanidinomesityl group occurs when treated with HBr/HOAc. The mesitylenesulfonyl group has also been used as a blocking group for other indoles. Boteju et al. reported the formation of the indole sulfonamide by treatment with n-Butyllithium and mesitylenesulfonyl chloride, but the sulfonamide group was not subsequently removed (eq 3).8

Sulfonate Formation.

Treatment of alcohols with mesitylenesulfonyl chloride yields the corresponding sulfonates. Mesitylenesulfonyl chloride is particularly useful for the selective sulfonation of polyhydroxylic systems such as carbohydrates (eq 4).1,9 It is more selective than p-Toluenesulfonyl Chloride, which has been frequently used but gives mixtures of products. Unfortunately, the mesitylenesulfonates are not as reactive as the corresponding tosylates. Numerous 1-derivatives of sucrose have been synthesized via mesitylenesulfonyl derivatives.10

The selectivity of sulfonation has also been applied to other polyhydroxylic systems such as a- and b-cyclodextrins11,12 and nucleotides.13 Monosulfonated products have been reported from the treatment of diols with mesitylenesulfonyl chloride (eq 5).14,15

Mesitylenesulfonyl derivatives which have specific biological activities, such as 2,3-diaziridinyl-1,4-napthoquinone sulfonates16 and 1-arenesulfonyloxy-2-alkanones,17 have also been prepared.

Nucleotide Synthesis.

Mesitylenesulfonyl chloride has been used as a condensing agent in the diester approach to nucleotide synthesis (eq 6).2 However, it is not effective in the triester approach due to extensive sulfonation of the 5-hydroxy group.18 Other condensing agents include 1,3-Dicyclohexylcarbodiimide (DCC), benzenesulfonyltriazole (BST), (1-mesitylyl-2-sulfonyl)-3-nitro-1,2,4-triazole (MSNT), Mesitylsulfonyl-1H-1,2,4-triazole (MST), p-nitrobenzenesulfonyltriazole (p-NBST), p-toluenesulfonyltriazole (TST), and triisopropylbenzenesulfonyl chloride (TPS).

Condensation Reactions.

Mesitylenesulfonyl chloride has also been employed as a condensing agent for the preparation of esters in the synthesis of nonactin (eq 7),19 N-methylmaysenine,20 and maysine.21

Sulfinate Ester Synthesis.

Sulfinate esters of menthol can be prepared via reaction of mesitylenesulfonyl chloride (as well as other sulfonyl chlorides) with menthol using Trimethyl Phosphite (eq 8).22 Sulfinate esters of menthol are used for the preparation of optically active sulfoxides. See also 10-Camphorsulfonyl Chloride and p-Toluenesulfonyl Chloride.

Sulfonylalkyne Synthesis.

Sulfonylalkynes have been synthesized (eq 9) and subsequently reacted with N-(1-alkynyl)anilines to give 2-anilino-5-sulfinylfurans.23

1. Guthrie, R. D.; Thang, S. AJC 1987, 40, 2133.
2. (a) Narang, S. A.; Khorana, H. G. JACS 1965, 87, 2981. (b) FF 1967, 1, 661.
3. (a) Reetz, M. T.; Kukenhohner, T.; Weinig, P. TL 1986, 27, 5711. (b) Pavlidis, V. H.; Chan, E. D.; Pennington, L.; McParland, M.; Whitehead, M. SC 1988, 18, 1615. (c) Hoppe, I.; Hoffmann, H.; Gartner, I.; Krettek, T.; Hoppe, D. S 1991, 1157. (d) Takahashi, H.; Takahashi, K.; Ohno, M.; Yoshioka, M.; Kobayashi, S. T 1992, 48, 5691.
4. Roemmele, R. C.; Rapoport, H. JOC 1988, 2367.
5. (a) Corey, E. J.; Weigel, L. O.; Floyd, D.; Bock, M. G. JACS 1978, 100, 2916. (b) FF 1980, 8, 318.
6. Fuji, N.; Futaki, S.; Yasumura, K.; Yajima, H. CPB 1984, 2660.
7. (a) Yajima, H.; Takeyama, M.; Kanaki, J.; Mitani, K. CC 1978, 482. (b) Yajima, H.; Takeyama, M.; Kanaki, J.; Nishimura, O.; Fujino, M. CPB 1978, 26, 3752.
8. Boteju, L. W.; Wegner, K.; Hruby, V. J. TL 1992, 7291.
9. Gilchrist, T. L.; Rees, C. W.; Stanton, E. CC 1971, 801.
10. Hough, L.; Phadnis, S. P.; Tarelli, E. Carbohydr. Res. 1975, 44, C12. (b) Ball, D. H.; Bisett, F. H.; Chalk, R. C. Carbohydr. Res. 1977, 55, 149. (c) Guthrie, R. D.; Jenkins, I. D.; Watters, J. J. AJC 1980, 33, 2487.
11. Fujita, K.; Matsunaga, A.; Imoto, T. JACS 1984, 106, 5740.
12. (a) Fujita, K.; Yamamura, H.; Imoto, T. JOC 1985, 50, 4393. (b) Fujita, K.; Ishizu, T.; Minamiura, N.; Yamamoto, T. CL 1991, 1889. (c) Fujita, K.; Ishizu, T.; Obe, K.; Minamiura, N.; Yamamoto, T. JOC 1992, 57, 5606.
13. (a) Ueda, T.; Usui, H.; Shuto, S.; Inoue, H. CPB 1984, 32, 3410. (b) Tanimura, H.; Sekine, M.; Hata, T. TL 1986, 27, 4047. (c) Xu, Y. Z.; Zheng, Q.; Swann, P. F. TL 1991, 24, 2817. (d) Xu, Y. Z.; Zheng, Q.; Swann, P. F. T 1992, 1729.
14. Nakata, T.; Fukui, M.; Ohtsuka, H.; Oishi, T. TL 1983, 24, 2661.
15. Rama Rao, A. V.; Gaitonde, A.; Prahlada Rao, S. IJC(B) 1992, 31B, 641.
16. Lin, T. S.; Xu, S. P.; Zhu, L. Y.; Cosby, L. A.; Sartorelli, A. C. JMC 1989, 32, 1467.
17. Ogawa, K.; Terada, T.; Muranaka, Y.; Hamakawa, T.; Hashimoto, S.; Fujii, S. CPB 1986, 34, 3252.
18. Katagiri, N.; Itakura, K.; Narang, S. A. JACS 1975, 97, 7332.
19. (a) Gerlach, H.; Oertle, K.; Thalmann, A.; Servi, S. HCA 1975, 58, 2036. (b) FF 1977, 6, 625.
20. Corey, E. J.; Weigel, L. O.; Floyd, D.; Bock, M. G. JACS 1978, 100, 2916.
21. Kitamura, M.; Isobe, M.; Ichikawa, Y.; Goto, T. JOC 1984, 49, 3517.
22. Sharpless, K. B.; Klunder, J. M. JOC 1987, 52, 2598.
23. Kosack, S.; Himbert, G. CB 1987, 120, 71.

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The Upjohn Co., Kalamazoo, MI, USA

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