Saccharinic acids amide

The principal IR absorptions of 3,20,23 5, and 913,18 (which compounds have been recommended for the identification of alcohols24 25 and primary or secondary amines18) and of 2-substituted saccharins (10)20,23 recorded under identical conditions appear as sets of relatively constant frequencies. For structures with an acidic hydrogen, e.g., compounds (l)16 (2), (9), self-association and complex formation is expected, but the dipolar 3-dialkylamino derivatives (5b) also tend to associate in various solvents.14 Saccharin (1) has been reported to form 1 1 complexes with purines, e.g., theophylline and caffeine, and with amides and... 

A major distinction for nucleophilic reactions with ambident anions is whether they proceed with kinetic or thermodynamic control.80 N-Substituted saccharins (10) should be thermodynamically more stable because of amide character than the isomeric pseudosaccharin (3) of imidate structure. In fact 3 may be rearranged thermally to 10 in an irreversible reaction.96 The threshold for thermodynamic control appears to be lowered for electrophiles with multiple bonds, e.g., formaldehyde, reactive derivatives of carboxylic acids, but also quaternary salts of N-heterocyclic compounds.80 It will be seen that in those cases substitution indeed occurs at the nitrogen, not necessarily through thermodynamic control. 

An alternative method involves a refined version of the Maumee process. Methyl anthranilate is initially diazotized to form 2-carbomethoxybenzenediazonium chloride sulfonation followed by oxidation then yields 2-carbomethoxybenzenesul-fonyl chloride. Amidation of this material, followed by acidification, forms insoluble acid saccharin. 

The intermediate sulfonimide derived from saccharin by addition of an alkyllithium compound is also the starting material for sultams mimicking the behavior of camphorsultams. The sultams arc readily obtained from, e.g., 3-methylbenzisothiazole 1,1-dioxide, by ruthenium-catalyzed enantioselective reduction, using BINAP as a chiral ligand, in enantiomerically pure form 79. Thus, both enantiomers can be obtained by using the appropriate enantiomer of the control ligand. Like the camphorsultams, the saccharin derivatives readily form amides with carboxylic acids which can be alkylated via the carbanion (Section D.1.1.1.3.1.) or, if unsaturated carboxylic acids are used, may react as chiral dienophiles in Diels—Alder reactions (Section D.l.6.1.1.1.). 

The product of sulphonation of toluene is a mixture of p- and o-toluensulphonic acids. The acids are converted into the sulphonyl chlorides, which may be separated, as the para compound is a solid and the ortho compound is a liquid. The liquid chloride is next converted by ammonia into the amide, which is oxidized in aqueous solution with potassium permanganate. On acidifying the solution saccharin is obtained. 

It is fortunate that the ortho acid chloride is the major product in the chlorosulfonation because it is needed in the synthesis of saccharin, the first of the non-fattening sweeteners. The formation of the sulfonamide is like that of an ordinary amide, but the oxidation of the methyl group with potassium permanganate is probably new to you. It s a rather vigorous reaction, but one which very usefully turns toluene derivatives into benzoic acid derivatives. 

Nitroso-piperidine—Nitro-toluene—Azo-benzene, introduction of hydroxyl groups — Toluene-sulphone-amides— Saccharine—p-Nitro-o-toluene-sulphone - amide—Oxida -tion of aromatic oxy-carboxylic acids.76-78... 

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