Oxathiazines

Acesulfame-K. Acesulfame-K [55589-62-3] (4), the potassium salt of acesulfame [33665-90-6] (6-methyl-l,2,3-oxathiaziQ-4(3ff)-one 2,2-dioxide), is a sweetener that resembles saccharin in stmcture and taste profile. 5,6-Dimethyl-l,2,3-oxathiazine-4(3ff)-one 2,2-dioxide, the first of many sweet compounds belonging to the dihydrooxathia2inone dioxide class, was discovered accidentally in 1967 (63). From these many sweet compounds, acesulfame was chosen for commercialisation. To improve water solubiUty, the potassium salt was made. Acesulfame-K (trade name Sunette) was approved for dry product use in the United States in 1988 and in Canada in October, 1994. Later, it was approved by the FDA for additional food categories such as yogurts, frosen and refrigerated desserts, and baked goods. 

Structurally related to saccharin are the oxathiazinone dioxides (104). Clauss and coworkers synthesized a series of these compounds, and demonstrated that they possess intense sweetness. Acesulfame-K, the potassium salt of 3,4-dihydro-6-methyl-l,2,3-oxathiazin-4-one 2,2-dioxide (104) has a sweetness intensity 130 times that of sucrose. 

The triazino-oxathiazines 559 were prepared by cyclocondensation of phenylhydrazone derivatives 558 with chlorosulfonyl isocyanate. The formation of 559 was dependent on the substituents (9ISC 1695). 

A novel method is reported to convert 1,3,5-oxathiazine-A-oxides 116 into 1,2,4-oxathiazoles 117 under thermal conditions. Lewis acid-promoted reaction of compounds 117 furnishes 1,2,4-thiadiazoles 118 and the final step is a type A synthesis (see Section 5.08.9.2) (Scheme 15) <2004HAC175>. 

Thiazetes are formed on the thermolysis of 4-aryl-2,2,6,6-tetra(triflu-oromethyl)-6//-l,3,5-oxathiazine. These thiazines are in thermally mobile equilibrium with (perfluoroisopropylidene)thiocarboxamide 224. The latter... 

Rhodium(II) catalyzed the addition of the carbene formed from methyl diazoacetoacetate, to the oxathiazolone (112 R = 4-MeOQH4) gives the 1,4,3-oxathiazine derivative (113) in low yield (6%), this probably proceeds through the intermediate sulfonium ylide (114), by decarboxylation and ring closure, either concominantly or sequentially (Scheme 14) <90JCR(S)343>. 

A novel synthesis in which diazoketones are thermolyzed with JV-sul-finylamines leads to cyclic S-oxides such as 3,4-dihydro-1,2,3-oxathiazine and 1,2-oxazetidine derivatives. A similar synthesis utilizing diazodiketones yields, via a 4 -f 2 cycloaddition, oxathiazines (165) and, via 2 -F 2 cycliza-tion, thiazetidines (166). When sulfonyldiazoketones were used, thiazetidines 167 were the only isolated products (Eq. 33). 

Burger et al. first introduced 2//-l,3-thiazete as a new heterocyclic system. By utilizing the stabilizing effect of trifluormethyl groups on strained-ring systems, they succeeded in reducing the size of a substituted oxathiazine ring to the thiazete system. The reaction proceeds via a thermally induced retro Diels-Alder mechanism with subsequent electrocyclization (Eq. 39). 

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