August 09, 2023p-Toluenesulfonyl chloride – description and application
p-Toluenesulfonyl chloride or tosyl chloride (TsCl) [98-59-9] is a derivative of toluene that contains a sulfonyl chloride functional group. It is a white, malodorous solid with the melting point of 68-69 °C[1] and the boiling point of 146 °C/15 mm Hg.[2] It is a skin, eye, and respiratory tract irritant. It reacts violently with water evolving hydrochloric acid. TsCl is corrosive substance that can cause injury to the skin, eyes, and respiratory tract and its inhalation may cause chemical pneumonitis.[3] Tosyl chloride is a moisture sensitive, corrosive lachrymator.
Preparation of p-Toluenesulfonyl chloride:
p-Toluenesulfonyl chloride can be easily prepared by chlorosulfonation of toluene.[4] It is a by-product from the production of ortho-toluenesulfonyl chloride (a precursor for the synthesis of the common food additive and catalyst saccharin).[5] Another possibility is oxidative chlorination of thiophenol with trichloroisocyanuric acid (TCCA) or N-chlorosuccinimide (NCS) in the presence of tetra-alkylammonium chloride.[6]
Application of p-Toluenesulfonyl chloride:
p-Toluenesulfonyl chloride is widely used reagent in organic synthesis. In characteristic manner, TsCl converts alcohols into the corresponding tosyl derivatives (tosylates) which are suitable for further substitution with nucleophiles. It has long been known that it is possible to selectively tosylate primary over secondary alcohols.[7] By proper choice of base it is possible to selectively O-tosylate in the presence of a free amine or N-tosylate in the presence of a free hydroxyl. It is used for the carboxyl activation of carbobenzoxy amino acids and peptides via the formation of mixed p-toluenesulfonic-carboxylic anhydrides.[8] Spontaneous Beckmann rearrangement has been observed upon O-tosylation of oximes. Lactams can therefore be conveniently prepared from cyclic oximes.[9]
Product categorization (Chemical groups):
Main category:
Second level:
Third level:
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[2] R. B. Woorward, I. J. Pachter, M. L. Scheinbaum Org. Synt. 1974, 54, 33. doi:10.15227/orgsyn.054.0033
[3] https://pubchem.ncbi.nlm.nih.gov/compound/P-Toluenesulfonyl-chloride#section=Safety-and-Hazards
[4] Y. Wang, Q. Zhang, J. Gong, X. Zhang Dyes Pigm. 2021, 189, 109261. doi:10.1016/j.dyepig.2021.109261
[5] C. A. DiPippo Method for preparing 2-sulfochloride benzoates and the use of same in the preparation of saccharin 1981, Image Products Group LLC, US4259499A.
[6] H. Veisi, A. Sedrpoushan, S. Hemmati, D. Kordestani Phosphorus Sulfur Silicon Relat. Elem. 2012, 187 (6), 769. doi:10.1080/10426507.2011.621910
[7] W. S. Johnson, J. C. Collins, R. Pappo, M. B. Rubin, P. J. Kropp, W. F. Johns, J. E. Pike, W. Bartmann J. Am. Chem. Soc. 1963, 85 (10), 1409. doi:10.1021/ja00893a012
[8] D. Theodoropoulos, J. Gazopoulos J. Org. Chem. 1962, 27 (6), 2091. doi:10.1021/jo01053a045.
[9] P. Oxley, W. F. Short J. Chem. Soc. 1948, 0, 1514. doi:10.1039/JR9480001514