Sulphonylations

NaOCHjCHa. White solid (Na in EtOH). Decomposed by water, gives ethers with alkyl halides reacts with esters. Used in organic syntheses particularly as a base to remove protons adjacent to carbonyl or sulphonyl groups to give resonance-stabilized anions. 

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... 

CeH5N(CH3)H + C SO C,H, -> CeH5N(CH3)S02C6H5 + HCl mono-and di-substituted derivatives of benzenesulphonamide, C6H5SO2NH2 and thus termed benzenesulphonphenylamide, and benzenesulphon-methylphenylamide respectively. Sulphonylation, like benzoylation, can there-... 

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. 

Meanwhile, filter the original cold reaction product at the pump, and wash the sulphonyl-methylaniline on the filter first with 10% sodium hydroxide solution (to ensure complete removal of the sulphonyl-aniline) and then with water drain thoroughly. Recrystallise from ethanol toluene-/)-sulphonyl-methylaniline, C H5N(CH3)S02C4H4CH3, is thus obtained as colourless crystals, m.p. 95° yield, 7-5 g. 

Finally, add an excess of concentrated hydrochloric acid slowly with stirring to the alkaline filtrate remaining from the original reaction product. As the solution becomes acid, the sulphonyl-aniline separates as a thick sticky syrup which, when stirred, rapidly crystallises. Cool the mixture in ice-water if necessary, and then filter off the solid product at the pump, wash well with water, and drain. Recrystallise from a mixture of 2 volumes of ethanol and i volume of water to prevent the sulphonyl-aniline from separating as an emulsion, allow the hot solution to cool spontaneously (with occasional stirring) until crystallisation starts, and... 

The aniline and the monomethylaniline can be obtained from their respective sulphonyl derivatives by hydrolysis with 70% sulphuric acid (preparation, p. 109), the mixture of the sulphonyl compound and the acid being gently boiled under reflux to illustrate the separation of the three amines, however, this is not necessary. 

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. 

Give benzoyl and toluene-/>-sulphonyl derivatives (Schotten-Baumann reaction) (p. 243) also benzene-sulphonyl derivatives. 

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.)... 

Note. PRIMARY ALIPHATIC AMINES. The lower amines are gases or low-boiling liquids (b.ps. CHjNH, 7 CiHjNH, 17 CH,(CH2,>,NH 49 (CHg)jCHNHa, 34 ) but may be encountered in aqueous or alcoholic solution, or as their crystalline salts. They are best identified as their benzoyl, or toluene-/>-sulphonyl derivatives (c/. (C) above), and as their picrates when these are not too soluble. This applies also to benzylamine, CjHsCHjNH, b.p. 185 also to ethylenediamine, usually encountered as the hydrate, NHj (CHj)j NH2,HjO, b.p. 116 , for which a moderate excess of the reagent should be used to obtain the di-acyl derivative. (M.ps., pp. 55 55 )... 

Benzoyl and Toluene -sulphonyl derivatives. Proceed as in 3 (p 374)- benzene sulphonyl derivatives can be similarly prepared. 

Note. The sulphonyl derivatives of secondary amines are neutral and insoluble in alkali, and separate on formation. (M.ps., p. 552.)... 

A) Picrates (except diphenylamine). (B) Acetyl Derivatives. (C) Benzoyl, Toluene-p sulphonyl and Benzenesulphonyl Derivatives. (D)... 

Primary and Secondary Amines. Picrates (pp. 374, 376), Acetyl derivatives (pp. 373, 376), Benzoyl derivatives (pp. 374, 376), Toluene-p-sulphonyl and benzene-sulphonyl derivatives (pp. 374, 376), Phenylurea derivatives (pp. 374, 377)-... 

Amino Aliphatic Carboxylic Acids. 3,5-Dinitrobenzoyl derivatives (p. 381), Benzoyl derivatives (p. 382), Sulphonyl derivatives (p. 382). 

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