Sulphonyl chlorides

A further difference between aliphatic and aromatic hydrocarbons is that only the latter are capable of direct sulphonation. Thus benzene when heated with concentrated sulphuric acid gives benzenesulphonic acid, a reaction which proceeds more readily, however, if chlorosulphonic acid is used instead of sulphuric acid an excess of chlorosulphonic acid however may convert the sul phonic acid into the sulphonyl chloride (c/. p. 181). 

ACETAMIDOBENZENESULPHONAMIDE. (Reac tion B.) Place the above crude damp sulphonyl chloride in a... 

The Schotten-Baumann reaction may also be carried out, using, for example, benzene sulphonyl chloride, CeH,SO,Cl (. e., the acid chloride of benzene sulphonic acid, C H5SOjOH) in place of benzoyl chloride, and similar deri a-tives are obtained. Thus when phenol is dissolved in an excess of 10% sodium hydroxide solution, and then shaken with a small excess of benzene sulphonyl... 

Although benzenesulphonyl chloride has for simplicity been used in the above discussion, tolucne-/>- sulphonyl chloride, CHaCeH SO Cl, is more frequently used in the laboratory, owing to its much lower cost, the latter being due in turn to the fact that toluene-p-sulphonyl chloride is a by-product in the commercial preparation of saccharin. Toluene-p sulphonyl chloride is a crystalline substance, of m.p. 68° the finely powdered chloride will, however, usually react readily with amines in the Schotten-Baumann reaction it does not react so readily with alcohols, but the reaction may be promoted considerably by first dissolving the chloride in some inert water-soluble solvent such as acetone. 

Required Phenol, 0-4 g. 10% sodium hydroxide, 2-5 ml. toluene-/)-sulphonyl chloride, 0-9 g. acetone, 4 ml. 

Required Aniline, 4 ml. monomethylaniline, 4 ml. dimethyl-aniline, 4 ml. toluenc-/)-sulphonyl chloride, 16 g. 

A) Toluene -sulphonates. For directions, using an acetone solution of toluene-/) Sulphonyl chloride, see p. 249 use o 3-o 5 g. of the phenol. Note that the chloride should be dissolved in a minimum of acetone, otherwise separation of the ester may be slow and incomplete. 

Z>) Toluene-p-sulphonylotion (p. 247). Proceed as in 3(a), but using 1 5 g of toluene-p-sulphonyl chloride, either finely pow dered or in concentrated acetone solution. Note. The sulphonyl derivative of a primary amine is soluble in aqueous sodium hydroxide, and the final solution must be diluted and acidified to precipitate the product. Recrystallise and take the m.p. (M.ps., pp. 550-551.)... 

Benzene-sulphonylotion. Benzene-sulphonyl chloride, which can be used in place of toluene-/>-sulphonyl chloride, is liquid at room temperature and consequently reacts rapidly when the reaction mixture (as in 3(a)) is vigorously shaken. In general, however, the toluene-/>-sulphonyl derivatives crystallise even more readily than the benzene-sulphonyl analogues, and have lower solubilities and higher m.ps. 

C) Benzoyl and Toluene-sulphonyl Derivatives. Proceed as in (3) above, using benzoyl or toluene p-sulphonyl chlorides benzene"Sul-phonyl chloride can be similarly used (see 3 above). (M.ps., pp. 550 -551.)... 

Almost insoluble in cold water. Higher alcohols (including benzyl alcohol), higher phenols (e.g., naphthols), metaformaldehyde, paraldehyde, aromatic aldehydes, higher ketones (including acetophenone), aromatic acids, most esters, ethers, oxamide and domatic amides, sulphonamides, aromatic imides, aromatic nitriles, aromatic acid anhydrides, aromatic acid chlorides, sulphonyl chlorides, starch, aromatic amines, anilides, tyrosine, cystine, nitrocompounds, uric acid, halogeno-hydrocarbons, hydrocarbons. 

C.H.[0].S.Halogen Aryl sulphonyl chlorides C.H.[0].N.S Salts of amines and nitro- ... 

Reaction with chlorosulphonic acid ( chlorosulphonyl-ation ). Sulphonamides. Many aryl hahdes, either alone or in chloroform solution, when treated with excess of chlorosulphonic acid afford the corresponding sulphonyl chlorides in good yield (compare Section IV.106) the latter may be readily converted into the aryl sulphonamides by reaction with concentrated ammonia solution or with sohd ammonium carbonate. 

The following give abnormal results when treated with chlorosulphonio acid alone, preferably at 50° for 30-60 minutes —fluobenzene (4 4 -difluorodiplienyl-sulphone, m.p. 98°) j iodobenzene (4 4 -di-iododiphenylsulplione, m.p. 202°) o-diclilorobenzene (3 4 3. -4 -tetrachlorodiphenylsulphone, m.p. 176°) and o-dibromobenzene (3 4 3 4 -tetrabromodiphenylsulphone, m.p. 176-177°). The resulting sulphones may be crystallised from glacial acetic acid, benzene or alcohol, 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 6N sodium hydroxide solution the sulphonamides dissolve readily and are reprecipitated by 6iV hydrochloric acid. 

Procedure 1. Dissolve 1 g. of the compound in 5 ml. of chloroform in a test-tube and cool in ice. Add 5 ml. of chlorosulphonic acid CA UTION in handhng) dropwise and with shaking. When the initial evolution of hydrogen chloride subsides, remove the reaction mixture from the ice and, after 20 minutes, pour it into a 50 ml. beaker filled with crushed ice. Separate the chloroform layer, wash it well with water, and evaporate the solvent. Recrystallise the residual aryl sulphonyl chloride from light petroleum (b.p. 40-60°), chloroform or benzene this is not essential for conversion into the sulphonamide. 

Procedure 2. Follow Procedure 1 except that no solvent is employed. Pour the s3Tupy reaction mixture on to crushed ice, remove the resulting aryl sulphonyl chloride and/or sulphone, if a sohd, by filtration with suction and, if a hquid, by means of a small separatory funnel or dropper, and wash with water. 

To convert the aryl sulphonyl chloride into the sulphonamide, use either of the following methods —... 

Sulphonamides. Mix together 1 0 g. of the dry acid or 1 - 2 g. of the anhydrous salt with 2 5 g. of phosphorus pentachloride f and heat under a reflux condenser in an oil bath at 150° for 30 minutes. Cool the mixture, add 20 ml. of dry benzene, warm on a steam bath and stir the solid mass well to extract the sulphonyl chloride filter. Add the benzene solution slowly and with stirring to 10 ml. of concentrated ammonia solution. If the sulphonamide precipitates, separate it by filtration if no solid is obtained, evaporate the benzene on a steam bath. Wash the sulphonamide with a little cold water, and recrystallise from water, aqueous ethanol or ethanol to constant m.p. 

The procedure is not usually applicable to aminosulphonic acids owing to the interaction between the amino group and the phosphorus pentachloride. If, however, the chlorosulphonic acid is prepared by diazotisation and treatment with a solution of cuprous chloride in hydrochloric acid, the crystalline chlorosulphonamide and chlorosulphonanilide may be obtained in the usual way. With some compounds, the amino group may be protected by acetylation. Sulphonic acids derived from a phenol or naphthol cannot be converted into the sulphonyl chlorides by the phosphorus pentachloride method. 

The sulphonanilldes may be prepared by either of the following methods —(i) Reflux the solution of the sulphonyl chloride in benzene obtained as above, with 2 5 g. of aniline for 1 hour. Concentrate the benzene solution to half its volume and cool in ice. Collect the solid which separates on a filter, wash with hot water, and recrystallise from ethanol or dilute ethanol. 

The melting points of the derivatives of a number of selected sulphonic acids are collected in Table IV,33 the melting points of the corresponding sulphonyl chlorides are included for purposes of reference. 

Add Sulphon- amlde, ArSO,NH, S-Benzyl- iio-thl- uronlum Salt Sulphon- anlllde ArSO,NHPh />-Tolul- dlne Salt Sulphonyl Chloride ArSO,CI... 

Acid Sulphon- amlde ArSO.NH, S-Benzyl- iro-thl- uronlum Salt Sulphon- anlUde ArSO.NHPh p-Tolul- dine Salt Sulphonyl Chloride, ArSO,Cl... 

Sulphonlc Acid B.P. Sulphonyl chloride, b.p. Sulphon- amlde, m.p. i -Benzyl-f ro-thluron-lum salt, m.p. Sulphon- anlllde, m.p. 

The sulphonyl chlorides are treated with concentrated ammonia solution to produce sulphonamides, which usually possess sharp melting points and are therefore useful as derivatives, for example ... 

Mix 1 0 g. of the phenol with 2 5 ml. of pyridine, add 2 g. of p-toluene-sulphonyl chloride, and heat on a water bath for 15 minutes. Pour into 25 ml. of cold water and stir until the oil solidifies. Filter, wash with cold dilute hydrochloric acid (to remove pyridine), with cold dilute sodium hydroxide solution (to remove any phenol present), and then with cold water. Recrystallise from methyl or ethyl alcohol. 

One method of preparing sulphlnic acids has already been described (diazo reaction. Section IV,65). Reduction of a sulphonyl chloride with zinc powder and water affords the zinc salt of the sulphinic acid, converted by sodium carbonate to the sodium salt (in which form it is conveniently isolated), and by hydrochloric acid into the somewhat unstable sulphinic acid, for example ... 

Thiophenols (or aryl mercaptans) are obtained by more vigorous reduction of sulphonyl chlorides (or of sulphinic acids), for example with zinc and dilute sulphuric acid, and are isolated by steam distillation ... 

---