Reduction sulphonamides

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. 

The imides, primaiy and secondary nitro compounds, oximes and sulphon amides of Solubility Group III are weakly acidic nitrogen compounds they cannot be titrated satisfactorily with a standard alkaU nor do they exhibit the reactions characteristic of phenols. The neutral nitrogen compounds of Solubility Group VII include tertiary nitro compounds amides (simple and substituted) derivatives of aldehydes and ketones (hydrazones, semlcarb-azones, ete.) nitriles nitroso, azo, hydrazo and other Intermediate reduction products of aromatic nitro compounds. All the above nitrogen compounds, and also the sulphonamides of Solubility Group VII, respond, with few exceptions, to the same classification reactions (reduction and hydrolysis) and hence will be considered together. 

Reduction to S(IV) is the basis of two spot tests of Feigl, although these apply to other S(VI) classes, e.g. sulphonamides. Thus Feigl and Lenzer fused the sample with alkali to yield sulphite, then treating with hydrochloric acid and warming to expel sulphur dioxide they detected the latter with nickel(II) hydroxide on test paper, which yielded ultimately the black Ni(IV) oxyhydrate (see also Section C). In the other test FeigF fused the sample with sodium formate/alkali, cooled and acidified with sulphuric acid to liberate sulphur dioxide in this case also. This was detected by a ferric chloride/potassium ferricyanide reagent which yielded a blue colour (Prussian, Turnbull s). 

The photochemical deprotection of sulphonamides to free amines is synthetically useful193. This process is caused by electron transfer from an electron-donating sensitizer such as 1,2-dimethoxybenzene or 1,4-dimethoxybenzene and the presence of reductants like ammonia or hydrazine is also required194 (equation 139). 

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%). 

Polyhydroxy- phenols. amino acids, di- and polyamino compounds, amino alcohols. Sulphonic acids. Sulphinic acids. Salts. sulphinic acids, aminosulphonic acids and sulphonamides. Some diketones and /3-keto esters. Ethers and acetals. Lactones. Acyl halides. Diaryl ethers. intermediate reduction products of nitro compounds. Sulphones, sulphonamides of secondary amines, sulphides, sulphates and other sulphur compounds. 

When j6-toluenesulphonyl azide was heated at 50-80° in isopropyl alcohol in the presence of diethyl peroxydicarbonate (20-3 azide 1 -4 peroxide), -toluenesulphonamide and acetone were obtained in 75 and 81% yields respectively " . It was thought that the 2-hydroxy-t-propyl radical (292) added to the azide to give 293 (equation 132) and that an intramolecular reduction and elimination of nitrogen occurred via a cyclic intermediate (294) to give the radical (295) and acetone. Hydrogen abstraction by (295) would then give the sulphonamide. 

Inhibition of folic acid synthesis in susceptible microorganisms and ultimately the synthesis of nucleic acids. By competing with para-aminobenzoic acid (PABA) for the enzyme dihydropteroate synthetase, sulphonamides prevent the incorporation of PABA into dihydrofolate, while trimethoprin, by selectively inhibiting dihydrofolate reductase, prevents the reduction of dihydrofolate to tetrahydrofolate (folic acid). Animal cells, unlike bacteria, utilize exogenous sources of folic acid. Pyrimethamine inhibits protozoal dihydrofolate reductase, but is less selective for the microbial enzyme and therefore more toxic than trimethoprim to mammalian species. 

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