Cyclohexylsulfamate

Before a 1/1 /70 FDA ban (rescission proposed in early 1990), cyclamate noncaloric sweeteners were the major derivatives driving cycloliexylamine production. The cyclohexylsulfamic acid sodium salt (39) [139-05-9J and mote thermally stable calcium cyclohexylsulfamic acid (40) [139-06-1] salts were prepared from high purity cyclohexylamine by, among other routes, a reaction cycle with sulfamic acid. 

Sulfation andSulfamation. Sulfamic acid can be regarded as an ammonia—SO. complex and has been used thus commercially, always in anhydrous systems. Sulfation of mono-, ie, primary and secondary, alcohols polyhydric alcohols unsaturated alcohols phenols and phenolethylene oxide condensation products has been performed with sulfamic acid (see Sulfonation and sulfation). The best-known appHcation of sulfamic acid for sulfamation is the preparation of sodium cyclohexylsulfamate [139-05-9] which is a synthetic sweetener (see Sweeteners). 

Sulfamation is the formation (245) of a nitrogen sulfur(VI) bond by the reaction of an amine and sulfur trioxide, or one of the many adduct forms of SO. Heating an amine with sulfamic acid is an alternative method. A practical example of sulfamation is the artificial sweetener sodium cyclohexylsulfamate [139-05-9] produced from the reaction of cyclohexylamine and sulfur trioxide (246,247) (see Sweeteners). Sulfamic acid is prepared from urea and oleum (248). Whereas sulfamation is not gready used commercially, sulfamic acid has various appHcations (see SuLFAMiC ACID AND SULFAMATES) (249—253). 

In the presence of a large excess of acid, sulfones such as diphenyl sulfone [127-63-9] (C H )2S02, can be formed (see Sulfolanes and sulfones). Sulfamation forms a —C—N—S— bond as in sodium cyclohexylsulfamate [139-03-9], C H NHSO Na, (see Sulfamic acid and sulfamates). Reviews of chlorosulfuric acid reactions are available (21,22). 

Therapeutic Function Nonnutritive sweetener Chemical Name Cyclohexylsulfamic acid calcium salt Common Name —... 

The residue from the distillation was evaporated to dryness in a vacuum oven at 50°C and the resulting product analyzed. The product weighing 105.5 parts by weight, 0.488 equivalent, was obtained which is a 98% yield of the technical calcium cyclohexylsulfamate dIhydrate. 

Cyclamates are the salts of the cyclohexylsulfamic acid. In 1969 cyclamates were blamed for being carcinogenic following a study in which an increase in bladder tumours was observed in a study on a cyclamate-saccharin blend. Following publication of the study the FDA and a number of other health authorities banned cyclamate from use in foods and beverages. On the basis of additional studies it has meanwhile been accepted that cyclamate is not carcinogenic. 

Cyclamate is a name for a group of compounds that include cyclamic (/V-cyclohexylsulfamic) acid, sodium cyclamate, and calcium cyclamate (Fig. 1). Audrieth and Sevda discovered this compound accidentally in 1937. It is a white crystalline powder with the molecular formula... 

Chemical Name Cyclohexylsulfamic acid calcium salt... 

SYNS CALCIUM CYCLAMATE CALCIUM CYCLO-HEXANESULFAMATE CALCIUM CYCLOHEXANE SULPHAMATE CALCIUM CYCLOHEXYLSULFAMATE CYCLAMATE CALCIUM CYCLAMATE, CALCIUM SALT CYCLAN CYCLOHEXANESULFAMIC ACID, CALCIUM SALT CYCLOHEXYLSULPHAMIC ACID, CALCIUM SALT CYLAN DIETIL KALZIUMZY-KLAMATE (GERMAN) SUCARYL CALCIUM... 

SYNS CYCLAMATE CYCLAMIC ACID CYCLO-HEXANESULPHAMIC ACID CYCLOHEXYLAMIDO-SULPHURIC ACID CYCLOHEXYLAMINESULPHONIC ACID CYCLOHEXYLSULFAMIC ACID (9CI) CYCLOHEXYLSULPHAMIC ACID HEXAiMIC ACID SUCARYL SUC RYL ACID... 

Cyclamate (cyclohexylsulfamic acid and its calcium and sodium salts) were discovered in the United States in 1937. They are 30 to 80 times as sweet as sucrose and were widely used until late 1969, when it was... 

Water-insoluble salts may also be prepared using ion-exchange resins. Metal drug salts, in contrast to organic salts, may be problematic with respect to taste because of their alkalinity. Salts incorporating the sweet-tasting A-cyclohexylsulfamic acid (cyclamate) as the counterion can render bitter drugs such as dextromethorphan and chlorpheniramine palatable. ... 

Gruber, C.M., Jr. Stephens, V.C. Tirrell, P.M. Propoxyphene napsylate chemistry and experimental design. Toxicol. Appl. Pharmacol. 1971, July, 19 (3), 423 26. Campbell, J.A. Slater, J.G. Modification of physical properties of certain antitussive and antihistaminic agents by formation of A-cyclohexylsulfamate salts. J. Pharm. Sci. 1962, Oct, 51, 931-934. 

Cyclohexylsulfamic acid monosodium salt E952 sodium cyclohexanesulfamate. 

Synonyms calcium N-cyclohexylsulfamate dihydrate Cyclan cyclohexanesulfamic acid calcium salt cyclohexylsulfamic acid calcium salt E952 Sucaryl calcium. 

Ammonium phenylsulfamate 11 may be reduced to ammonium cyclohexylsulfamate over rhodium catalyst, at room temperature . 

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