Para-Toluenesulfonyl chlorides

Para-toluenesulfonyl chloride (9.6 g, 50 mmol) is added slowly at 0°C to a mixture of (—)-(2R,4R)-2,4 pentanediol (2.1 g, 20 mmol) and dry pyridine (16 mL, 200 mmol). A suspension forms and the mixture is stirred for 16 h. Ether (50 mL) and 200 mL crushed ice is then added with vigorous stirring. The two phases separate and the organic layer is washed, in turn, with 50 mL portions of 5% aqueous HC1,1% aqueous NaHC03, and distilled water and... 

The first step in the synthesis of saccharin is an electrophilic substitution reaction, like the first step of the benzocaine synthesis, but this time we want the orf/ro-substituted product. Chloro-sulfonic acid gives a mixtiue of ortho and para products—it is impossible to find conditions that completely avoid forming the para-toluenesulfonyl chloride. However, you may recognize an old friend here—the by-product is, of course, TsCl. You may have wondered why we always use TsCl and not PhS02Cl to make OH into a leaving group now you know. 

To a solution of the amide (1.15 g, 3.6 mmol) and para-toluenesulfonyl chloride (1.91 g, 7.2 mmol) in CH2CI2 (9 mL) was added pyridine (1.46 mL, 18 mmol). After complete reaction, as judged by TLC, saturated aqueous NaHCOs was carefully added. 

Several sulfonyl chlorides are available to activate OH groups. The most common one is para-toluenesulfonyl chloride. 

It is fairly easy to convert an alcohol into a tosylate by treating it with para-toluenesulfonyl chloride, so this would be an alternative way of converting the poor OH leaving group into a good leaving group. 

For primary and secondary alcohols, the hydroxyl is best made into a leaving group for elimination reactions by sulfonylation with para-toluenesulfonyl chloride (tosyl chloride, TsCl) or methanesulfonyl chloride (mesyl chloride, MeS02Cl or MsCl). 

Scheme 11.49. A synthesis of periplanone A (after Hauptmann, H. Mtlhlbauer, G. Sass, H. Tetrahedron Lett., 1986, 6189). LDA = lithium diisopropyl amide p-TsCl = para-toluenesulfonyl chloride NaHMDS = sodium hexamethyldisilazide DMAP = 4-dimethyl-aminopyridine TMSCl = trimethylchlorosilane PCC = pyridiniumchlorochromate TBHP = f-butyl hydrogen peroxide TBDMSCI = f-butyldimethylchlorosilane TBAF = tetrabutylammonium fluoride Cp = cyclopentenyl.

Several sulfonyl chlorides are available to activate OH groups. The most common one is para-toluenesulfonyl chloride (abbreviated as TsCl). The sulfonate ester formed from the reaction of TsCl and an alcohol is called an alkyl tosylate (abbreviated as ROTs). 

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