Toluene Toluenesulfonyl chloride

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... 

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. 

Piroxicam Piroxicam, 1,1 -dioxid-4-hydroxy-2-methyl-iV-2-pyradyl-2//-1,2-benzothiazine-3-carboxamide (3.2.78), is synthesized from saccharin (3.2.70). Two methods for saccharin synthesis are described. It usually comes from toluene, which is sulfonated by chlorosulfonic acid, forming isomeric 4- and 2-toluenesulfonyl chlorides. The isomeric products are separated by freezing (chilling). The liquid part, 2-toluenesulfonyl chloride (3.2.68) is separated from the crystallized 4-toluenesulfochloride and reacted with ammonia, giving 2-toluenesul-fonylamide (3.2.69). Oxidation of the product with sodium permanganate or chromium (VI) oxide in sulfuric acid gives saccharin—o-sulfobenzoic acid imide (3.2.70) [123-126]. 

In sharp contrast to the behavior observed when the three dithio-acetals aforementioned are treated with p-toluenesulfonyl chloride in pyridine, dialkyl dithioacetals of D-arabinose, treated under the same conditions, are converted into the corresponding 5-p-toluene-sulfonates, generally isolable crystalline in high yield.72 This remarkable difference has been interpreted72" on conformational grounds the D-arabinose dithioacetals are stable in the extended, planar zigzag conformation, whereas the other three examples experience some destabilization in the extended form, because of parallel 1,3-interactions.726 Furthermore, the transition state for closure of the 2,5-anhydro ring would be quite strained in the D-arabinose series, but not in the other three.72"... 

The clinical and commercial success of the antidepressant compound fluoxetine (Chapter 2 Prozac) engendered considerable work in other laboratories. A benzo-dioxan based compound that shows similar activity shares only a few stmctural features with the prototype. The benzodioxan nucleus (68-3) is formed by an alkylation reaction between the fluorocatechol (68-1) and the derivative (68-2) from meso, and hence achiral, butanetetrol. The benzyl protecting groups are then removed by hydrogenation over palladium, and the thus-obtained diol is converted to the fiii-toluene-sulfonate (68-4) by reaction with toluenesulfonyl chloride. Treatment of that intermediate with benzylamine leads to fiw-alkylation on the same nitrogen to form a pyrrolidine ring and thus the tricyclic compound (68-5). A second hydrogenolysis step then leads to fluparoxan (68-6) [70]. 

Sometimes, the sulfonyl chloride is dissolved in an indifferent, water-immiscible solvent. Thus, tosylation of cellulose was brought about by treating alkali-cellulose with a solution of p-toluenesulfonyl chloride in carbon tetrachloride,6061 benzene,61-64 or toluene.56 The number of... 

More recently, benzaldehydedisulfonic acid has been prepared, not from toluene, but from toluenesulfonyl chloride. This use, as well as others, has considerably increased the price of the previously ahnost worthless p-toluenesulfonyl chloride. 

Toluenesulfonyl azide was prepared from jj-toluene-sulfonyl chloride and sodium azide. The submitters found that when somewhat less than the stoichiometric quantity of -toluenesulfonyl azide is used, 2-diazocyelohexanone is obtained free of azide the excess 2-(hydroxymethylene)-cyclohexanone is readily removed in the alkaline workup. The crude product obtained by the checkers, however, contained -toluenesulfonyl azide (Note 5). 

Most commonly used are esters of / -toIuenesuIfonic acid the / -toluenesiil-fonates. The name of the / -toliienesulfonyl group is often shortened to tosyl (Ts) p-toluenesulfonyl chloride thus becomes tosyl chloride (TsCl), and p-toluene-sulfonates become tosylates (TsOR). 

Toluene is first treated with chlorosulfonic acid to form o- and p-toluenesulfonyl chlorides, which are separated. The o-sulfonyl chloride is then treated with ammonia to form the amide and finally the methyl group is oxidized to the carboxylic acid. The carboxyl and the amino groups are reacted to form a cyclic imide ... 

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. 

General Procedure for the Synthesis of2-(p-Toluenesulfonyl)alcanes. These were obtained from the corresponding 2-alcanols la-d (200 mmol, 1.0 equiv) dissolved in pyridine (135 mL) and cooled to 0 °C. /7-Toluenesulfonyl chloride (41.8 g, 220 mmol, 1.1 equiv) was slowly added and the mixture was stirred at room temperature overnight. Toluene was added (200 mL), die reaction mixture filtered, and the filtrate washed with toluene (200 mL). The mother liquor was washed twice with an aqueous HCl solution (5 N, 200 mL). The organic layer was dried over MgS04 and concentrated under reduced pressure. After dry chromatography on silica gel (pentane/EtOAc, 9 1, v/v), the 2-(p-toluenesulfonyl)alcanes 2a-d were obtained as colorless oils in 60-80% yields. 

A mixture of toluene 2c (5 mmol), p-toluenesulfonyl chloride 1 (5 mmol), and Zn dust (5 mmol) was ejqtosed to microwaves for 45 s or heated at 110°C for 60 min. After completion of reaction (TLC), the product 3 was extracted with ether (3x10 mL). Removal of the solvent under reduced pressure gave product in good yield and in pure form. In most of the cases, the reaction works very well on 25 mmol scale. 

When 4-amino-5-methyl-l-(p-toluenesulfonyl)benzotriazole (283) was boiled in toluene for 3 h, rearrangement into 7-methyl-4-[(p-toluenesul-fonyl)amino]benzotriazole (284) was complete. However, the same compound was boiled in benzene for 1.5 h and produced a trace of 284. The bis-tosylate 285 was stable in nonpolar solvents and its rearrangement to 286 was accelerated on raising the temperature. No rearrangement of 285 to 286 was observed in chloroform and it was slow in toluene. No rearrangement from 286 to 285 was observed in DMSO-d6 at room temperature (92JOC190). Furthermore, when 4-aminobenzotriazole 287 was treated with one equivalent of p-toluenesulfonyl chloride in pyridine, 4-[(p-tolu-enesulfonyl)amino]benzotriazole (288) was obtained either by the rearrangement of the 1-sulfonyl-substituted compound or by its direct formation. Compound 288 was stable when heated in toluene for 5 h (Scheme 92). 

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