Sulphonamides, preparation

Dichloramine-T(jV,jV-dichlorotoluene-p-sulphonamide). Prepare about 200 ml of a saturated solution of calcium hypochlorite by grinding a fresh sample of bleaching powder with water and filtering with slight suction. Dissolve 5 g (0.029 mol) of toluene-p-sulphonamide in as small a volume of the calcium hypochlorite solution as possible (about 150 ml) and filter the solution if necessary. Cool in ice, and add about 50 ml of a mixture of equal volumes of glacial acetic acid and water slowly and with stirring until precipitation is complete. The dichloramine-T separates out first as a fine emulsion, which... 

Erythema nodosum, encountered in 5% of children with tuberculosis. This rate increased to 45% if a sulphonamide preparation (sulphathiazole) was administered (Rollof 1950). 

Sulphonamides.—Preparations of sulphonamides from sulphonyl halides are illustrated with examples of particular interest from the recent literature, viz. a-bromoalkanesulphonaraides RCHBrS02NHBu and iV-alkyl-lViV-... 

NHCOCH3. White crystals, m.p. 18l-l83"C. Soluble sulphacetamide is the sodium salt which is soluble in water. Il is prepared by acetylating sulphanilamide and hydrolysing one acetyl group. Being more soluble than most of the sulphonamides it is used in treating infections of the urinary tract and of the conjunctiva. 

C10H10N4O2S. White powder, which darkens on exposure to light m.p. 255-256 C. Prepared by condensing p-acet-amidobenzenesulphonyl chloride with 2-aminopyrimidine and subsequent hydrolysis. Soluble sulphadiazine is the sodium salt. Sulphadiazine is the least toxic of the more potent sulphonamides. ... 

Dissolve log. of powdered toluene-p-sulphonamide in 6o ml. of 10% aqueous sodium hydroxide (2 5 mols.) diluted with 50 ml. of water to moderate the reaction. Then, using the same precautions as in the previous preparation, add 127 ml. (17 g., 2 3 mols.) of dimethyl sulphate and shake the mixture vigorously. The crystalline dimethylamide rapidly separates from the warm... 

The acidic properties of sulphonamides and their mono-substitution derivatives are particularly well illustrated in the alkyl ubstitution compounds, which by reason of these properties can be prepared by two distinct methods. Thus mono- and di-ethylamine, when subjected to the Schotten-Baumann reaction using benzenesulphonyl chloride, gi e benzenesulphonethylamide, and bcnzenesulphondiethylamide respectively. These compounds can also... 

Dichloramine-T. Dilute 80 ml, of freshly prepared 2N sodium hypochlorite soluticMi (preparation, p. 525) with 80 ml. of w ter, and then add with stirring 5 g. of finely powdered toluene-p-sulphonamide, a clear solution being rapidly obtained. Cool in ice-water, and then add about 50 ml. of a mixture of equal volumes of glacial acetic acid and water slowly with stirring until precipitation is complete the dichloro-amide separates at first as a fine emulsion, which rapidly forms brittle colourless crystals. Filter off the latter at the pump, wash well with... 

The best results are obtained with freshly prepared xanthhydrol (reduction of xanthone with sodium amalgam. Section VII,16). Dissolve 0 -25 g. of xanthhydrol and 0 -25g. of the primary sulphonamide in 10 ml. of glacial acetic acid. Shake for 2-3 minutes at the laboratory temperature and allow to stand for 60-90 minutes. Filter oflf the derivative, recrystallise it from dioxan-water (3 1), and dry at room temperature under water pump suction for 30 minutes. 

All reactions employing diazomethane must be carried out in a well-ventilated hood behind a safety screen. After observing the appropriate precautions, diazomethane is safely prepared by the base treatment of N-methyl-N nitroso-p-toluene sulphonamide ( Diazald ). 

The sulphonamides are prepared by the action of concentrated aqueous solution of NH3 on sulphonyl chlorides. 

The sulphonamides are used in the preparation of chloramines which are good disinfectants. Ring substituted sulphonamides are used in the preparation of sulphadrugs. 

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 ... 

The stock solutions of sulphonamides were prepared by dissolving 100 mg of the compounds in 100 ml methanol. These solutions were stored at +4°C and were used to prepare a standard solution (1 mg.l ). This solution was stored at +4°C. 

The palladium catalysed addition of N-H or O-H bonds onto allenes has successfully been exploited in the preparation of oxazepines, diazepines, oxazocines and diazocines. The nucleophilic attack of the pendant alcohol or sulphonamide function on the allene moiety was followed by the incorporation of the alcohol, used as solvent, to give the desired cyclic products in good yield (5.15. and 5.16.). The bromoallene in these processes is the synthetic equivalent of an allylic dication.15... 

An ethereal solution of diazomethane is usually prepared immediately before it is required for reaction. A convenient precursor for the generation of diazomethane is IV-methyl-lV-nitrosotoluene-p-sulphonamide which is prepared by the action of nitrous acid on N-methyltoluene-p-sulphonamide. This latter is formed from toluene-p-sulphonyl chloride and methylamine in alkaline solution. The methylnitrosamide affords diazomethane on reaction with potassium hydroxide solution. 

The strong characteristic i.r. absorption of the S02 (or SO) group exhibited by all these compounds is clearly apparent in the spectrum of toluene-p-sulphonamide (Fig. 3.40). In addition, the absorption arising from the presence of the OH, Cl, NH2 or OR groups is usually easily assigned. The confirmation of aromatic substitution patterns by inspection of the p.m.r. spectra is described in the preparative examples below, wherein the fragmentation patterns observable in the m.s. are also discussed. 

Chloramine-T (sodium N-chlorotoluene-p-sulphonamide). For this preparation use dichloramine-T which has been prepared as above and thoroughly drained but not necessarily dried. Heat 45 ml of 10 per cent aqueous sodium hydroxide solution in a beaker to a temperature of about 80 °C, add 3.5 g (0.015 mol) of dichloramine-T in small quantities, stirring the mixture gently after each addition until a clear solution is obtained. When the addition is complete, filter the hot solution if turbid, and then allow it to cool spontaneously. Filter the crystals with suction, wash with a little saturated sodium chloride solution and dry upon filter paper or in a desiccator over anhydrous calcium chloride. The resulting chloramine-T weighs 3g (75%) and is almost pure. It may be recrystallised, if desired, from twice its weight of hot water. 

Formation of sulphonamides. These may be prepared as described for Aromatic hydrocarbons, Section 9.6.3, p. 1238. 

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 chloro-sulphonamide and chlorosulphonanilide may be obtained in the usual way. With some compounds, the amino group may be protected by acetylation. Sul-phonic acids derived from a phenol or naphthol cannot be converted into the sulphonyl chlorides by the phosphorus pentachloride method. 

Sulphonacetamides are derivatives of sulphonamides (Section 9.6.27, p. 1286), but since the latter are readily prepared from the sulphonic acids or their salts, sulphonacetamides may be employed for the characterisation of sulphonic adds for this reason they are included in this Section. 

The authors noted an earlier communication describing (290) and the analogous sulphonamide derivative i.e., -SOzGluH, which did not, however, describe the method of preparation P.C. Edwards, D. Starling, A.M. Mattocks and H.E. Skipper, Science (Washington, DC), 107 (1948) 119. 

Lowe et al. [7] and Frias et al. [8] described complexes of cyclene-based molecules with lanthanoids. A gadolinium complex which would exhibit pH-dependent relaxivity thanks to a switch in hydration state was prepared. [7] Cyclene bore a sulphonamide substituent in order to achieve a variation of the coordination environment of the lanthanide centre as a function of pH (Scheme 7). 

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