Toluene-o-sulphonamide

C (decomp.) It is made by the oxidation of toluene-o-sulphonamide with alkaline permanganate. Saccharin has about 550 times the sweetening power of sucrose, and is used extensively as a sweetening agent, usually in the form of the sodium salt. The use of saccharin is restricted in the U.S. 

The sweetening agent saccharin is also derived from a sulphonamide it is prepared from toluene-o-sulphonamide by oxidising the CHs-group to carboxyl with permanganate ring closure is subsequently brought about by the action of concentrated hydrochloric acid ... 

Toluene-o-sulphonamide is an intermediate in the synthesis of saccharin (Expt 6.42). Upon oxidising toluene-o-sulphonamide with potassium permanganate in alkaline solution, the sodium salt of o-sulphonamidobenzoic acid is formed, which on acidification with concentrated hydrochloric acid passes spontaneously into the cyclic imide of o-sulphobenzoic acid or saccharin. Saccharin itself is sparingly soluble in cold water, but the imino hydrogen is acidic and the compound forms a water-soluble sodium salt. The latter is about 500 times as sweet as cane sugar. 

Place 20g (0.105mol) of toluene-o-sulphonyl chloride (Expt 6.41) in a large evaporating dish mounted on a water bath. Add powdered ammonium carbonate cautiously with stirring until the mass is quite hard and solid and the unpleasant odour of the sulphonyl chloride has disappeared. Allow to cool, and extract with cold water to remove the excess of ammonium carbonate. Recrystallise the crude toluene-o-sulphonamide first from hot water (add a little decolourising carbon if it is dark in colour) and then from ethanol. The yield of pure product, m.p. 154°C, is 16 g (89%). 

Oxidation of toluene-o-sulphonamide to saccharin. In a 600-ml beaker, mounted on an electric hot plate and provided with a mechanical stirrer, place 12 g (0.07 mol) of toluene-o-sulphonamide, 200 ml of water and 3g of pure sodium hydroxide. Stir the mixture and warm to 34-40 °C until nearly all has passed into solution (about 30 minutes). Introduce 19g (0.32 mol) of finely powdered potassium permanganate in small portions at intervals of 10-15 minutes into the well-stirred liquid. At first the permanganate is rapidly reduced, but towards the end of the reaction complete reduction of the permanganate is not attained. The addition occupies 4 hours. Continue the stirring for a further 2-3 hours, and then allow the mixture to stand overnight. Filter off the precipitated manganese dioxide at the pump and decolourise the filtrate by the addition of a little sodium metabisulphite solution. Exactly neutralise the solution with dilute hydrochloric acid (use methyl orange or methyl red as external indicator). Filter off any o-sulphonamidobenzoic acid (and/or toluene-o-sulphonamide) which separates at this point. Treat the filtrate with concentrated hydrochloric acid until the precipitation of the saccharin is complete. Cool, filter at the pump and wash with a little cold water. Recrystallise from hot water. The yield of pure saccharin, m.p. 228 °C, is 7.5 g (58%). 

Plasticisers are comparatively uncommon but plasticised grades are supplied by some manufacturers. Plasticisers lower the melting point and improve toughness and flexibility, particularly at low temperatures. An example of a plasticiser used commercially in Santicizer 8, a blend of o- and p-toluene ethyl sulphonamide (Figure 18.18). 

Toluene-/ sulplionamide is almost insolubb in cold water, but dissolves readily in sodium hydroxide solution (as the sodium derivative) aid is immediately reprecipitated on the addition of strong acids. To show the formation of the sodium derivative, dissolve about o-2 g. of metallic sodium in about 10 ml, of ethanol, cool the solution, and then add it to a solution of 1 g. of the sulphonamide in 20 ml. of cold edianol. On shaking the mixture, fine white crystals of the sodium derivative, CH,C,HjSO,NHNa, rapidly separate, and may be obtained pure by filtering at the pump, and washing firet with a few ml. of ethanol, and then with ether. 

During the discussions of a potential carcinogenicity of saccharin, contaminants, especially o-toluene sulphonamide, were blamed for the toxicological effects observed in these studies. The studies carried out on such contaminants which in former times occurred in concentrations well exceeding 1000 ppm, did, however, not reveal any such effects, and the observed effects today are believed to be saccharin-specific. In order to minimise risks for consumers, low maximum levels for these products were introduced into the specifications. 

Primary amino acids will react with o-phthalaldehyde in the presence of the strongly reducing 2-mercaptoethanol (pH 9-11) to yield a fluorescent product (emission maximum, 455 nm excitation maximum, 340 nm). Peptides are less reactive than a-amino acids and secondary amines do not react at all. As a result, proline and hydroxyproline must first be treated with a suitable oxidizing agent such as chloramine T (sodium A-chloro-p-toluene-sulphonamide) or sodium hypochlorite, to convert them into compounds which will react. Similarly cystine and cysteine should also be first oxidized to cysteic acid. 

The mixture of o- and p-toluenesulphonyl chlorides produced from toluene may be separated by cooling to — 10° to — 20° when most of the p-isomer, which is a solid, m.p. 69°, separates out. Both isomers may be easily converted (e.g., by treatment with solid ammonium carbonate or with concentrated ammonia solution) into the corresponding highly crystalline sulphonamides which may be employed for interesting syntheses. 

The following give abnormal results when treated with chlorosulphonic acid alone, preferably at 50 °C for 30-60 minutes fluorobenzene (4,4 -difluoro-diphenylsulphone, m.p. 98 °C) iodobenzene (4,4 -diiododiphenylsulphone, m.p. 202 °C) o-dichlorobenzene (3,4,3, 4 -tetrachlorodiphenylsulphone, m.p. 176 °C) and o-dibromobenzene (3,4,3, 4 -tetrabromodiphenylsulphone, m.p. 176— 177 °C). The resulting sulphones may be crystallised from glacial acetic acid, toluene or ethanol, and are satisfactory for identification of the original aryl halide. In some cases sulphones accompany the sulphonyl chloride they are readily separated from the final sulphonamide by their insolubility in cold 6 m sodium hydroxide solution the sulphonamides dissolve readily and are reprecipitated by 6 m hydrochloric acid. 

The sulphonamide (0.171 g, 1 mmol) and 2-nitrosotoluene (0.121 g, 1 mmol) were stirred in dichloromethane (50 ml) at room temperature until a homogeneous solution was obtained. DIB (0.322 g, 1 mmol) was added and the resulting solution was stirred for 18 h. The reaction mixture was washed with cold saturated sodium bicarbonate solution (2 x 50 ml) and water (1 x 50 ml), dried and concentrated the residue was purified by column chromatography (silica gel, hexane-chloroform, 7 3) to give p-toluenesulphonyl-AWO-azoxy-o-toluene (143 mg, 52%) m.p. 82-83°C. 

---