Name: Saccharin
CAS No: 1,2-Benzisothiazol-3(2H), one 1,1-dioxide [81-07-2]
BP: Saccharin JP: Saccharin PhEur: Saccharin USP-NF: Saccharin
1,2-Benzisothiazolin-3-one 1,1-dioxide; benzoic acid sulfimide; benzoic sulfimide; benzosulfimide; 1,2-dihydro-2-ketobenzisosulfonazole; 2,3-dihydro-3-oxobenzisosulfonazole; E954; Garantose; gluside; Hermesetas; sacarina; saccarina; saccharin insoluble; saccharinum; o-sulfobenzimide; o-sulfobenzoic acid imide.
1,2-Benzisothiazol-3(2H), one 1,1-dioxide [81-07-2]
C7H5NO3S 183.18
Saccharin is an intense sweetening agent used in beverages, food products, table-top sweeteners, and oral hygiene products such as toothpastes and mouthwashes. In oral pharmaceutical formulations, it is used at a concentration of 0.02–0.5% w/w. It has been used in chewable tablet formulations as a sweetening agent.(1,2) Saccharin has been used to form various pharmaceutical cocrystals.(3) Saccharin can be used to mask some unpleasant taste characteristics or to enhance flavor systems. Its sweetening power is approximately 300–600 times that of sucrose
Saccharin occurs as odorless white crystals or a white crystalline powder. It has an intensely sweet taste, with a metallic or bitter aftertaste that at normal levels of use can be detected by approximately 25% of the population. The aftertaste can be masked by blending saccharin with other sweeteners.
See Table I
Acidity/alkalinity pH = 2.0 (0.35% w/v aqueous solution) Density (bulk) 0.7–1.0 g/cm3 Density (tapped) 0.9–1.2 g/cm3 Dissociation constant pKa = 1.6 at 258C Heat of combustion 3644.3 kJ/mol (871 kcal/mol) Moisture content 0.1% NIR spectra see Figure 1. Solubility Readily dissolved by dilute ammonia solutions, alkali hydroxide solutions, or alkali carbonate solutions (with the evolution of carbon dioxide).
Saccharin can react with large molecules, resulting in a precipitate being formed. It does not undergo Maillard browning
Saccharin is prepared from toluene by a series of reactions known as the Remsen–Fahlberg method. Toluene is first reacted with chlorosulfonic acid to form o-toluenesulfonyl chloride, which is reacted with ammonia to form the sulfonamide. The methyl group is then oxidized with dichromate, yielding o-sulfamoylbenzoic acid, which forms the cyclic imide saccharin when heated. 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-carbomethoxybenzenesulfonyl chloride. Amidation of this material, followed by acidification, forms insoluble acid saccharin.
There has been considerable controversy concerning the safety of saccharin, which has led to extensive studies since the mid-1970s. Two-generation studies in rats exposed to diets containing 5.0–7.5% total saccharin (equivalent to 175 g daily in humans) suggested that the incidence of bladder tumors was significantly greater in saccharin-treated males of the second generation than in controls.(5,6) Further experiments in rats suggested that a contaminant of commercial saccharin, o-toluene sulfonamide, might also account for carcinogenic effects. In view of these studies, a ban on the use of saccharin was proposed in several countries. However, in 1977 a ban by the FDA led to a Congressional moratorium that permitted the continued use of saccharin in the USA. From the available data it now appears that the development of tumors is a sex-, species-, and organ-specific phenomenon, and extensive epidemiological studies have shown that saccharin intake is not related to bladder cancer in humans.(7,8) The WHO has set a temporary acceptable daily intake for saccharin, including its calcium, potassium, and sodium salts, at up to 2.5 mg/kg body-weight.(9) In the UK, the Committee on Toxicity of Chemicals in Food, Consumer Products, and the Environment (COT) has set an acceptable daily intake for saccharin and its calcium, potassium, and sodium salts (expressed as saccharin sodium) at up to 5 mg/kg body-weight.(10) Adverse reactions to saccharin, although relatively few in relation to its widespread use, include: urticaria with pruritus following ingestion of saccharin-sweetened beverages(11) and photosensitization reactions.(12) LD50 (mouse, oral): 17.5 g/kg(13) LD50 (rat, IP): 7.10 g/kg LD50 (rat, oral): 14.2 g/kg
Observe normal precautions appropriate to the circumstances and quantity of material handled. Eye protection and a dust mask are recommended.
Accepted for use as a food additive in Europe. Note that the EU number ‘E954’ is applied to both saccharin and saccharin salts. Included in the FDA Inactive Ingredients Database (oral solutions, syrups, tablets, and topical preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.
Acesulfame potassium; alitame; aspartame; isomalt; lactilol; maltitol; mannitol; neotame; saccharin ammonium; saccharin calcium; saccharin sodium; sodium cyclamate; sorbitol; sucralose; tagatose; thaumatin; xylitol.
Saccharin ammonium Empirical formula C7H8N2O3S Molecular weight 200.2 CAS number [6381-61-9] Saccharin calcium Empirical formula C14H8CaN2O6S23H2O Molecular weight 467.48 CAS number [6381-91-5] for the hydrated form [6485-34-3] for the anhydrous form Synonyms Syncal CAS. Appearance White, odorless crystals or crystalline powder with an intensely sweet taste. Solubility 1 in 4.7 ethanol (95%); 1 in 2.6 of water.