Saccharin reduction

When saccharin is treated with diethyl phosphorothiolothionate, the 3-ethylmercapto compound is obtained, rather than the expected organophosphorus compound (77 ACS(B)460). Treatment of saccharin with phosphorus pentoxide and amines gives 3-(substituted-amino)-1,2-benzisothiazole 1,1-dioxides, via an intermediate phosphate (81ZN(B)1640). Reduction of saccharin with zinc and hydrochloric acid gives 2,3-dihydro-l,2-benzisothiazole 1,1-dioxide, the method being used to estimate saccharin in foodstuffs (75MI41701). 

Saccharin, 2-methyl-reduction, 6, 152 Saccharin, 6-nitro-reduction, 6, 154 Saccharin, thio-hydrolysis, 6, 161 methylation, 6, 160 Safranines applications, 3, 196 Safrole derivatives toxicity, 1, 139-140 occurrence, 6, 781 Safrole, 1-hydroxy-toxicity, 1, 140 Salazosulfapyridine... 

V-Acylsaccharins prepared by treatment of the sodium salt of saccharin with acyl chlorides were reduced by 0.5 molar amounts of sodium bis(2-methoxyethoxy)aluminum hydride in benzene at 0-5° to give 63-80% yields of aliphatic, aromatic and unsaturated aldehydes [1108 Fair yields (45-58%) of some aliphatic aldehydes were obtained by electrolytic reduction of tertiary and even secondary amides in undivided cells fitted with platinum electrodes and filled with solutions of lithium chloride in methylamine. However, many secondary and especially primary amides gave 51-97% yields of alcohols under the same conditions [130]. 

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%). 

Although many substances have been produced by oxidation methods anthraquinone, vanillin, saccharin oxidation is not so easily graduated as the reduction processes. The overvoltage of oxygen is relatively high at most anodes, and frequently the compound to be oxidised is decomposed during treatment and carbon dioxide formed. 

The exocyclic carbonyl group of isothiazol-3-ones absorbs in the region 1610-1660 cm-1 (71JHC591). 2-Methylisothiazol-3-one itself has the C=0 and C=C bands at 1660 and 1629 cm-1, respectively, in CCLt solution (64TL1477). The low carbonyl frequency is due in part to contributions from the resonance form (20b). The carbonyl frequency increases in sulfoxides (1660-1730 cm-1) and 1,1-dioxides (1690-1740 cm-1) where such forms are not favourable. Sulfoxides (1060-1190 cm-1) and sulfones (1330-1360 and 1150-1190 cm-1) absorb in the regions expected (e.g. saccharin, 1353 and 1162 cm-1), but resonance forms related to (13) cause a reduction of the frequency of the asymmetric S02 vibration to near 1280 cm-1 (70CB3166). A similar situation arises in 3-amino-l,2-benzisothiazole 1-oxides. 

Preparative Methods both enantiomers of the a-methyl sultam may be prepared on a multigram scale in optically pure form by asymmetric hydrogenation of imine (2a) followed by simple crystallization (eq 1). The (7 )-enantiomer of the a-f-butyl sultam may also be prepared in enantiomerically pure form by asymmetric reduction of imine (2b) followed by fractional crystallization. However, multigram quantities of either enantiomer of the a-t-butyl sultam may be prepared by derivati-zation of the racemic auxiliary (obtained in 98% yield from reaction of (2b) with Sodium Borohydride in MeOH) with 10-Camphorsulfonyl Chloride, separation of the resulting diastere-omers by fractional crystallization, and acidolysis. Prochi-ral imines (2a) and (2b) are readily prepared from inexpensive Saccharine by treatment with Methyllithium (73%) and t-Butyllithium (66%), respectively. 

At this stage, the possible presence of a branched-chain saccharinic acid in Kiliani s preparation was supported only by (a) the properties of the barium salt of the hydroxyhexanoic acid obtained from it on reduction and (b) the reported oxidation of parasaccharinic acid with nitric acid to a tribasic acid. The latter evidence was retracted by Kiliani in his final report on the matter, when he stated that the previous identification of hydroxycitric acid was in error and that this tribasic acid is, in fact, ( — )-tartaric acid. In addition, he now observed that oxidation of parasaccharinic acid with nitric acid, followed by reduction with hydriodic acid and red phosphorus, gives a low yield of adipic acid. 

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