Of saccharin

C (decomp.) It is made by the oxidation of toluene-o-sulphonamide with alkaline permanganate. Saccharin has about 550 times the sweetening power of sucrose, and is used extensively as a sweetening agent, usually in the form of the sodium salt. The use of saccharin is restricted in the U.S. 

Although benzenesulphonyl chloride has for simplicity been used in the above discussion, tolucne-/>- sulphonyl chloride, CHaCeH SO Cl, is more frequently used in the laboratory, owing to its much lower cost, the latter being due in turn to the fact that toluene-p-sulphonyl chloride is a by-product in the commercial preparation of saccharin. Toluene-p sulphonyl chloride is a crystalline substance, of m.p. 68° the finely powdered chloride will, however, usually react readily with amines in the Schotten-Baumann reaction it does not react so readily with alcohols, but the reaction may be promoted considerably by first dissolving the chloride in some inert water-soluble solvent such as acetone. 

Pseudo-saccharin ethers. Pseudo-saccharin chloride (Section VII,26) reacts with alcohols to give ethers (0 alkyl derivatives of saccharin) ... 

Pseudo-saccharin ethers. When pseudo-saccharin chloride is heated with an excess of a phenol, 0-aryl derivatives of saccharin are produced (compare Section 111,27, 7). 

Hydrolysis of saccharin (o-sulphobenzoic imide) (Section IV, 209) with dilute hydrochloric acid yields acid ammonium 0 sulphobenzoate, w hich upon... 

Other Uses. Other appHcations for sodium nitrite include the syntheses of saccharin [81-07-2] (see Sweeteners), synthetic caffeine [58-08-2] (22), fluoroaromatics (23), and other pharmaceuticals (qv), pesticides (qv), and organic substances as an inhibitor of polymerization (24) in the production of foam blowing agents (25) in removing H2S from natural gas (26) in textile dyeing (see Textiles) as an analytical reagent and as an antidote for cyanide poisoning (see Cyanides). 

Acesulfame-K is a white crystalline powder having a long (six years or more) shelf life. It readily dissolves in water (270 g/L at 20°C). Like saccharin, acesulfame-K is stable to heat over a wide range of pH. At higher concentrations, there is a detectable bitter and metallic off-taste similar to saccharin. Use of the sodium salt of feruHc acid [437-98-4] (FEMA no. 3812) to reduce the bitter aftertaste of acesulfame-K has been described (64). The sweetness potency of acesulfame-K (100 to 200x, depending on the matching sucrose concentration) (63) is considered to be about half that of saccharin, which is about the same as that of aspartame. 

In 1969, a chronic toxicity study on a cyclamate saccharin (10 1) blend indicated bladder cancer problems in rats. Cyclamate was soon banned by the FDA, but saccharin remained an approved sweetener. In 1977, the FDA proposed a ban on saccharin because of the discovery of bladder tumors in some male rats fed with high doses of saccharin. Because no other nonnutritive sweetener was available at that time, the proposed ban faced strong opposition. 

The main utihty of saccharin had been in beverages and as a table-top sweetener. Upon the approval of aspartame for carbonated beverages in 1983, aspartame displaced saccharin in most caimed and bottied soft drinks. However, saccharin is stiU used, usually blended with aspartame, in carbonated soft drinks dispensed from soda fountains. 

Saccharin is the most economical sweetener available. It is 300 times (8% sucrose solution sweetness equivalence) more potent than sugar and its price in 1996 was about 6.05/kg, ca 0.02/(kg-sweet unit). Sugar, on the other hand, was ca 0.77/kg, which is 39 times more expensive than saccharin on equal sweetness basis. Consequentiy, the low cost and high stabiUty of saccharin render it the sweetener of choice for dentifrices (qv), other toiletry products, and pharmaceuticals (qv). 

Many analogues of saccharin have been synthesized since its discovery. With the exception of one compound, thieno[3,4-i/ isothiazolone dioxide [59337-79-0] lOOOX, this effort has not generated more potent compounds. Acesulfame-K could be considered a ring-modification derivative of saccharin, however. 

In addition to a continued increase in the number of use patents in these fields, a new use of xanthates as inhibitors of fertiliser nitrogen transformation in soil has been reported, as well as the use of certain metal xanthates as color developers for image-recording materials (113,114) (see Fertilizers Color photography). For several years, sodium isopropyl xanthate was used as an intermediate in the manufacture of saccharin (see... 

Both Watts and sulfamate baths are used for engineering appHcation. The principal difference in the deposits is in the much lower internal stress obtained, without additives, from the sulfamate solution. Tensile stress can be reduced through zero to a high compressive stress with the addition of proprietary sulfur-bearing organic chemicals which may also contain saccharin or the sodium salt of naphthalene-1,3,6-trisulfonic acid. These materials can be very effective in small amounts, and difficult to remove if overadded, eg, about 100 mg/L of saccharin reduced stress of a Watts bath from 240 MPa (34,800 psi) tensile to about 10 MPa (1450 psi) compressive. Internal stress value vary with many factors (22,71) and numbers should only be compared when derived under the same conditions. 

Benzisothiazoles suffer straightforward ring cleavage, but their 1,1-dioxides, 2,1-benzisothiazoles and derivatives of saccharin give products containing no sulfur. 

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). 

Manufacturing qualifiers. Two of the entries to the section 313 chemical list contain a qualifier relating to manufacture. For isopropyl alcohol, the qualifier is "manufacturing-strong acid process. For saccharin, the qualifier simply is "manufacturing." For isopropyl alcohol, the qualifier means that only facilities which manufacture isopropyl alcohol by the strong acid process are required to report. In the case of saccharin, only manufacturers of the chemical are subject to the reporting requirements. A facility that processes or otherwise uses either chemical would not be required to report for those chemicals. In both cases, supplier notification does not apply because only manufacturers, not users, of the toxic chemical must report. 

Fig. 4 Explanation of the fluorescence-quenching effect [2]. — (A) chromatograms of the same quantities of saccharin and dulcin observed under UV 254 light, (B) schematic representation of fluorescence quenching, (C) spectral reflectance curves of saccharin and dulcin.

KMn04, an oxidizer, decolorizer, bleacher and purificalion agent its major application is in the manufacture of saccharin. 

The most widely used variant of the Gabriel-Colman is the conversion of saccharine derivatives to benzothiazine derivatives. The reaction has been extensively studied as benzothiazines are important pharmacophores, particularly in the oxicam class of antiinflammatories. The first reported instance of this transformation was in 1956 where 43 was treated with sodium methoxide to provide 44. The rearrangement also works with esters " and some amides " in addition to ketones. 

The mechanism of this variant of the Gabriel-Colman reaction has been investigated. Treatment of saccharine derivatives 45-48 with 1-2 equivalents of sodium alkoxide at room temperature provides esters 49-52 in good yields treatment of 45-48 with sodium alkoxide at reflux provides the expected benzothiazines 53-56. Increased concentration leads to higher yields. 

For example, if saccharin (33) is methylated in benzene suspension, then only iV-methylsaccharin is isolated. If an ethereal saccharin solution is added to a concentrated solution of diazomethane in excess, then 10% of 0-methylsaecharin (34) can be detected in addition to the A"-raethy] derivative. Finally, if the diazomethane solution is gradually added to a saturated ethereal solution of saccharin, the proportion of 0-methylation increases to 24%. " ... 

For high diazomethane concentrations, the Sn2 reaction, Eq. (7), and thus A—methylation occurs, whereas 0-methylation is favored by lower diazomethane concentrations, Eq, (6) (for an interpretation of this effect, according to Arndt, see references 33 and 42). The extent of this effect is limited by the constitution of the lactam in question. The fact that the addition of the sodium salt of saccharin to the reaction mixture leads to increased A -mcthylation for saccharin can be taken as supporting the foregoing interpretation. 

Two new pyridone derivatives (14) and (15) have been prepared by cycloaddition of saccharin pseudochloride (16 R = Cl) with Danishefsky s diene and by treatment of (16 R = Me) with ciimamoyl chloride. The synthesis of two more ting expanded derivatives (17) and (18) via cycloaddition to benzisothiazoles was also described <96T3339>. 

The taste of various amino acids, sugars, and aliphatic nitro compounds was studied, and it was concluded that the distance over which this hydrogen atom migrates, to give a second tautomeric form, determines the sweetness. In the case of saccharin, the sweetness was explained as due to two tautomeric forms. 

The taste of saccharin was further studied, and it was found that (1) the alkaline-earth-metal salts are sweet, whereas the heavy-metal salts are astringent (2) the sweet taste is lost if the sulfimide ring is cleaved, or if... 

Moncrief summarized the work of Cohn and the information in the early literature. As early as 1923, it was known that rupture of the heterocyclic ring, as well as substitution of the imino hydrogen atom, results in the loss of sweetness. Thus, o-carboxybenzenesulfonamide and N-alkyl derivatives of saccharin are tasteless. This loss of sweetness would be expected, as the NH group is the only proton-donor function available in the molecule. 

Such a grouping would be expected to exhibit tautomerism, as in 110, 111, and 112, and Beets concluded that the presence either of the tautomeric groups 110 and 111 or the mesomeric group 112 is a sufficient condition for bitterness. The bitterness of the thio analog (102) of saccharin is presumably attributable to the same phenomenon, as it exists in tautomeric forms and has no hydrogen-donor group. ... 

---