Toluenesulfonyl chlorides

Handling, Storage, and Precautions freshly purified tosyl chloride should be used for best results. Tosyl chloride is a moisture-sensitive, corrosive lachrymator. 

General Discussion. The tosylation of alcohols is one of the most prevalent reactions in organic chemistry. Optimized conditions for this reaction include the use of a 1 1.5 2 ratio of al-cohol/tosyl chloride/pyridine in chloroform (eq 1). This procedure avoids formation of unwanted pyridinium salts inherent to reactions where higher relative quantities of pyridine have been employed.  

Solubility insol H2O freely sol ethanol, benzene, chloroform, ether. 

Form Supplied in white solid, widely available. 

Purification upon prolonged standing the material develops impurities of p-toluenesulfonic acid and HCl. Tosyl chloride is purified by dissolving 10 g in a minimum volume of CHCI3 (ca. 25 mL), filtering, and diluting with five volumes (ca. 125 mL) of petroleum ether (bp 30-60 °C) to precipitate impurities (mostly tosic acid, mp 101-104 °C). The solution is filtered, clarified with charcoal, and concentrated to ca. 40 mL by evaporation. Further evaporation to a very small volume gives 7 g of pure white crystals (mp 67.5-68.5 °C).  

The reaction of toluene and excess chlorosulfonic add produces a mixture of tolu-ene-2- and toluene-4-sulfonyl chloride. At low temperatures (approx. 0 °C) the formation of the 2-isomer is favored, whereas at high temperatures a concentration of the 4-isomer of around 80% can be obtained. The isomers can be separated by distillation or by crystallization. 

Toluene-2-sulfonyl chloride is converted into the corresponding sulfonamide, which, after an oxidation step, is used in the production of the sweetener saccharin. 

Toluene-2-sulfonyl chloride Toluene-4-sulfonyl chloride 

The content of 2-sulfonamide, a suspected carcinogen, is limited in commercial saccharin to 10-25 ppm, varying from country to country. 

Saccharin can also be produced from anthranilic acid by way of dithiosodium-salicylate. 

Todd Whitaker, K. Sinclair Whitaker Carl R. Johnson Wayne State University, Detroit, MI, USA 

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If the temperature is not kept below 25°C dunng the reaction of primary alcohols with p toluenesulfonyl chloride in pyndine it is sometimes observed that the isolated product is not the desired alkyl p toluenesulfonate but is instead the corresponding alkyl chlonde Suggest a mech anistic explanation for this observation... 

Conversion to p toluenesulfonate es ters (Section 8 14) Alcohols react with p toluenesulfonyl chloride to give p toluenesulfonate esters Sulfo nate esters are reactive substrates for nucleophilic substitution and elimma tion reactions The p toluenesulfo nate group is often abbreviated —OTs... 

The reaction of alcohols with acyl chlorides is analogous to their reaction with p toluenesulfonyl chloride described earlier (Section 8 14 and Table 15 2) In those reactions a p toluene sulfonate ester was formed by displacement of chloride from the sulfonyl group by the oxygen of the alcohol Carboxylic esters arise by displacement of chlonde from a carbonyl group by the alcohol oxygen... 

Fig. 4. Glaxo synthesis of and where ]>TsCl = -toluenesulfonyl chloride and Py = pyridine (24).

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. 

Acid YeUow 23 (31), commonly known as Tartraziae, stiU maintains sales of nearly 0.5 million /yr ia the United States. It was first discovered ia 1884 and is made by coupling equimolar quantities of diazotized sulfarulic acid to 3-carboxy-l- -sulfophenyl)-5-pyrazolone. Other monoazopyrazolone dyes of commercial importance iaclude Acid YeUow 17 (32) (sulfarulic acid — l-(2,5-dichloro-4-sulfophenyl)-3-methyl-5-pyrazolone and Acid YeUow 40 [6372-96-9] (33) (Cl 18950) (p-aminophenol l-(4-chloro-2-sulfophenyl)-3-methyl-5-pyrazolone) foUowed by esterification of the phenoUc hydroxy group with -toluenesulfonyl chloride. 

Other disazo dyes with good substantivity and high wet-fastness properties on polyamides are Acid Red 114 (40), made by coupling o-toHdine to phenol which is then coupled to G-acid, followed by reaction of the phenoHc hydroxyl group with -toluenesulfonyl chloride, and Acid Blue 113 (41) (metanilic acid — 1-naphthylamine — 8-anilino-1-naphthalenesulfonic acid). 

Other methods for preparing -chlorotoluene include cx-elimination from an organoteUurium(IV) halide (57), paHadium-cataly2ed decarbonylation of 4-methylben2oyl chloride (58), and desulfonylation of -toluenesulfonyl chloride cataly2ed by chlorine (59) or cblorotris(tripbenylpbospbine)rbodium (60). 

Dichlorotoluene (l,3-dichloro-2-methylben2ene) is prepared from the Sandmeyer reaction on 2-arnino-6-chlorotoluene. Other methods include ring chlorination of -toluenesulfonyl chloride followed by desulfonylation (81), and chlorination and dealkylation of 4-/ f2 -butyltoluene (82) or... 

Tetrachlorotoluene, C H Cl (mol wt 229.93) (1,2,3,5-tetrachloro-4-methylben2ene), is prepared from the Sandmeyer reaction on 3-arnino-2,4,6-trichlorotoluene. 2,3,4,5-Tetrachlorotoluene (l,2,3,4-tetrachloro-5-methylben2ene) is the principal isomer in the further chlorination of 2,4,5-trichlorotoluene. Exhaustive chlorination of -toluenesulfonyl chloride, followed by hydrolysis to remove the sulfonic acid group yields... 

The 2- and 4-monochloro and 2,4- and 3,4-dichlorobenzyl chloride, benzal chloride, and benzotrichlorides are manufactured by side-chain chlorination of the appropriate chlorotoluene. -Chlorobenzotrichloride (1 -chioro-4-trichioromethylhenzene) can be prepared by peroxide-catalyzed chlorination of -toluenesulfonyl chloride or di-/)-toluylsulfone (71). 2,4-Dichlorobenzotrichloride (1,3-dich1 oro-4-trichi oromethylhen zene) is obtained by the chlorination of 2-chloro-4-chlorosulfonyltoluene (72). 

Toluenesulfonylhydrazide has been prepared by shaking 50% hydrazine hydrate and / -toluenesulfonyl chloride in benzene for several hours. Ammonia has been used as an agent for removing the hydrogen chloride evolved. ... 

In a typical case, ethylamine is allowed to react with ethylene oxide to produce N-ethyldiethanolamine (5). The latter is then treated with additional ethylene oxide to afford N,N-di(polyoxyethylene)ethylamine (6) where the sum a -t b is 3. This material is then stirred at room temperature for 3 h with toluenesulfonyl chloride and powdered sodium hydroxide in dioxane solution. After filtration and Kugelrohr distillation, N-eth-ylmonoaza-15-crown-5 is isolated in 75% yield as illustrated below in Eq. (4.7). 

Selective hydroxylation with osmium tetroxide (one equivalent in ether-pyridine at 0 ) converts (27) to a solid mixture of stereoisomeric diols (28a) which can be converted to the corresponding secondary monotoluene-sulfonate (28b) by treatment with /7-toluenesulfonyl chloride in methylene dichloride-pyridine and then by pinacol rearrangement in tetrahydrofuran-lithium perchlorate -calcium carbonate into the unconjugated cyclohepte-none (29) in 41-48 % over-all yield from (27). Mild acid-catalyzed hydrolysis of the ketal-ketone (29) removes the ketal more drastic conditions by heating at 100° in 2 hydrochloric acid for 24 hr gives the conjugated diketone (30). 

In the reaction with enamino ketones derived from dimedone (e.g., 49) p-toluenesulfonyl chloride gives the chloroiminium cation (138) isolated as the perchlorate. This indicates that initial O sulfonation is followed by addition of chloride ion and subsequent expulsion of tosylate (42) in a manner similar to the trichloroacetyl chloride reaction with 49 (Section IV.A). 

The reaction of p-toluenesulfonyl chloride (TsCl) with 1-hydroxytryptamines was expected to follow the same reaction pathways as that of MsCl described in Section IV.B. 1. In fact, it is different from the expectation (2000H2487). Thus, 39 reacts with TsCl in THF to provide 49a (42%), 51a (6%), 53a (3%), 60 (0.5%), and... 

From l-cyclohexyl-3-ethyldiaziridine, crystalline derivatives have been prepared with p-toluenesulfonyl chloride and with 3,5-dinitro-benzoyl chloride, e.g., 46/ The quantitative liberation of iodine from acid iodide solution characterizes these compounds as true diaziridines. 

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