Ortho-toluenesulfonyl chloride

Toluenesulfonyl Chloride. Toluene reacts with chlorosulfonic acid to yield both ortho- and j )i7n7-toluenesulfonyl chlorides, of which Monsanto is the only producer. The ortho isomer is converted to saccharin. 

Lx)ng-chain fatty acid cellulose esters were synthesized by the acid-chloride-pyridine reaction with different degrees of substitution. Hydrolyzed soybean oil was used as an unsaturated fatty acid [82]. The preparation of cellulose esters with substituted benzoic acids in the presence of p-toluenesulfonyl chloride in pyridine was investigated [83]. The substituents included NO2, Cl, Me, and MeO. The substituent and its position (ortho, meta, or para) did not influence the reaction significantly. 

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. 

Saccharin (84) was discovered in 1878 and can be manufactured from toluene (Scheme 18). In the synthesis, the initial chlorosulfonation yields a mixture of the o-and p-toluenesulfonyl chlorides the required ortho-isomer is obtained by freezing out the solid para-isomer to leave the liquid o-sulfonyl chloride behind. The imino hydrogen atom in saccharin is acidic owing to the electron-attracting (-1) properties of the adjacent carbonyl and sulfonyl moieties (Scheme 18). Consequently, saccharin readily forms the sodium salt, sodium saccharin (84), on treatment with sodium hydroxide. 

Initially, use was made of p-toluenesulfonyl chloride. However, the primary hydroxyl of the nucleoside may attack the phosphorus or sulfur atom of the anhydride intermediate, giving extensive sulfonation. This problem has been reduced by the introduction of steric bulk at the ortho positions of the benzene ring, thus favoring attack at the phosphorus atom. The commonly used derivatives are mesitylenesulfonyl chloride (MS) and 2,4,6-triisopropylbenzenesulfonyl chloride (TPS). 

Toluene 9 is more reactive towards sulfonation than benzene due to the electron-donating (+1) methyl group, and treatment with chlorosulfonic acid (two molar equivalents) at 0-5 °C yields a mixture of the ortho- (58%) and para-(14%) toluenesulfonyl chlorides 10 and 11 (Equation 37). 

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