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E 952 is an artificial sweetener.
E 952 is 30–50 times sweeter than sucrose (table sugar), making it the least potent of the commercially used artificial sweeteners.
E 952 is often used with other artificial sweeteners, especially saccharin; the mixture of 10 parts cyclamate to 1 part saccharin is common and masks the off-tastes of both sweeteners.
CAS: 139-05-9
MF: C6H14NNaO3S
MW: 203.23
EINECS: 205-348-9
E 952 is less expensive than most sweeteners, including sucralose, and is stable under heating.
Safety concerns led to E 952 being banned in a few countries, though the European Union considers it safe.
Odorless or almost odorless white crystals or crystalline powder.
Intensely sweet taste, even in dilute solution.
pH (10% solution in water): 5.5-7.5. Used as a non-nutritive sweetener.
E 952 was discovered in 1937 at the University of Illinois by graduate student Michael Sveda.
Sveda was working in the lab on the synthesis of an antipyretic drug.
He put his cigarette down on the lab bench, and when he put E 952 back in his mouth, he discovered the sweet taste of E 952.
The patent for E 952 was purchased by DuPont and later sold to Abbott Laboratories, which undertook the necessary studies and submitted a New Drug Application in 1950.
Abbott intended to use E 952 to mask the bitterness of certain drugs such as antibiotics and pentobarbital.
In 1958, E 952 was designated GRAS (Generally Recognized as Safe) by the United States Food and Drug Administration.
E 952 was marketed in tablet form for use by diabetics as an alternative tabletop sweetener, as well as in a liquid form.
As E 952 is stable to heat, it was and is marketed as suitable for use in cooking and baking.
In 1966, a study reported that some intestinal bacteria could desulfonate E 952 to produce cyclohexylamine, a compound suspected to have some chronic toxicity in animals.
Further research resulted in a 1969 study that found the common 10:1 cyclamate–saccharin mixture increased the incidence of bladder cancer in rats.
The released study was showing that eight out of 240 rats fed a mixture of saccharin and E 952, at levels equivalent to humans ingesting 550 cans of diet soda per day, developed bladder tumors.
Sales continued to expand, and in 1969, annual sales of E 952 had reached $1 billion, which increased pressure from public safety watchdogs to restrict the usage of cyclamate.
In October 1969, Department of Health, Education & Welfare Secretary Robert Finch, bypassing Food and Drug Administration Commissioner Herbert L. Ley, Jr., removed the GRAS designation from cyclamate and banned E 952's use in general-purpose foods, though it remained available for restricted use in dietary products with additional labeling; in October 1970, the FDA, under a new commissioner, banned cyclamate completely from all food and drug products in the United States.
Abbott Laboratories claimed that E 952's own studies were unable to reproduce the 1969 study's results, and, in 1973, Abbott petitioned the FDA to lift the ban on E 952.
This petition was eventually denied in 1980 by FDA Commissioner Jere Goyan.
Abbott Labs, together with the Calorie Control Council (a political lobby representing the diet foods industry), filed a second petition in 1982.
Although the FDA has stated that a review of all available evidence does not implicate cyclamate as a carcinogen in mice or rats, E 952 remains banned from food products in the United States.
The petition is now held in abeyance, though not actively considered.
E 952 is unclear whether this is at the request of Abbott Labs or because the petition is considered to be insufficient by the FDA.
In 2000, a paper was published describing the results of a 24-year-long experiment in which 16 monkeys were fed a normal diet and 21 monkeys were fed either 100 or 500 mg/kg E 952 per day; the higher dose corresponds to about 30 cans of a diet beverage.
Two of the high-dosed monkeys and one of the lower-dosed monkeys were found to have malignant cancer, each with a different kind of cancer, and three benign tumors were found.
The authors concluded that the study failed to demonstrate that cyclamate was carcinogenic because the cancers were all different and there was no way to link cyclamate to each of them.
E 952 did not show any DNA-damaging properties in DNA repair assays.
E 952 is the sodium or calcium salt of cyclamic acid (cyclohexanesulfamic acid), which itself is prepared by reacting freebase cyclohexylamine with either sulfamic acid or sulfur trioxide.
Prior to 1973, Abbott Laboratories produced E 952 (Sucaryl) by a mixture of ingredients including the addition of pure sodium (flakes or rods suspended in kerosene) with cyclohexylamine, chilled and filtered through a high speed centrifugal separator, dried, granulated and micro-pulverised for powder or tablet usage.
E 952 is hydrolyzed by sulfuric acid and cyclohexylamine at a very slow rate that is proportional to the hydrogen ion concentration.
Therefore, for all practical considerations, E 952 can be regarded as stable.
Solutions are also stable to heat, light, and air over a wide pH range.
Samples of tablets containing E 952 and saccharin have shown no loss in sweetening power following storage for up to 20 years.
The bulk material should be stored in a well-closed container in a cool, dry place.
E 952 Chemical Properties
Melting point: >300 °C (lit.)
Density: 1.58[at 20℃]
Vapor pressure: 0.002Pa at 150℃
Storage temp.: room temp
Solubility: 200g/l
Form: Powder
Color: White
PH: 5.5-7.5 (100g/l, H2O, 20℃)
Water Solubility: >=10 g/100 mL at 20 ºC
Merck: 14,2703
BRN: 4166868
InChIKey: UDIPTWFVPPPURJ-UHFFFAOYSA-M
LogP: -2.63 at 20℃
CAS DataBase Reference: 139-05-9(CAS DataBase Reference)
IARC: 3 (Vol. Sup 7, 73) 1999
EPA Substance Registry System: E 952 (139-05-9)
Uses
E 952 is an artificial sweetener and is 30 times as saccharose's.
E 952 is widely used in pickles, seasoning sauce, cakes, biscuits, bread, ice cream, frozen sucker, popsicles, drinks and so on, with a maximum amount of 0.65g/kg.
Secondly, E 952 is used in confect, with a maximum amount of 1.0g/kg.
Thirdly, E 952 is used in orange peel, preserved plum, dried arbutus and so on, with the largest amount of 8.0g/kg.
E 952 is also used in cosmetics and pharmaceutical industry.
E 952 (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 E 952 was banned by the FDA because of questions on safety.
E 952 is not banned in Canada and the European Union.
E 952 is produced by reacting cyclohexylamine with sulfonating agents, followed by reactions with sodium or calcium hydroxides to produce cyclamates and free cyclohexylamine as follows.
Owing to their good stability, E 952 is suitable for all applications of intense sweeteners without a significant interfering taste sensation, and are heat stable.
The main application of E 952 is in blends with saccharin in a 10:1 ratio by weight.
The mixture is more than twice as sweet as either component alone, making them an important sweetener in countries approving the use of both sweeteners.
Pharmaceutical Applications
E 952 is used as an intense sweetening agent in pharmaceutical formulations, foods, beverages, and table-top sweeteners.
In dilute solution, up to about 0.17% w/v, the sweetening power is approximately 30 times that of sucrose.
However, at higher concentrations E 952 is reduced and at a concentration of 0.5% w/v a bitter taste becomes noticeable.
E 952 enhances flavor systems and can be used to mask some unpleasant taste characteristics.
In most applications, E 952 is used in combination with saccharin, often in a ratio of 10 : 1.
Toxicology
E 952 is an odorless powder.
E 952 is about 30 times as sweet as sucrose in dilute solution.
The structure of E 952 is shown in Figure 10.10 Capillary transitional cell tumors were found in the urinary bladders of 8 out of 80 rats that received 2600 mg/kg body weight per day of a mixture of E 952 and sodium saccharin (10:1) for up to 105 weeks.
When the test mixture was fed at dietary levels designed to furnish 500, 1120, and 2500 mg/ kg body weight to groups of 35 and 45 female rats, the only significant finding was the occurrence of papillar carcinomas in the bladders of 12 of 70 rats fed the maximum dietary level of the mixture (equivalent of about 25 g/kg body weight) for periods ranging from 78 to 105 weeks (except for one earlier death).
In vivo conversion from E 952 to cyclohexylamine was observed particularly in the higher dosage group.
E 952 is very toxic (LD50 rat oral＝157 mg/dg) compared to E 952 (LD50 oral＝12g/kg).
Production Methods
After sulfonating cyclohexylamine with chlorosulfonic acid or sulfamate to cyclohexylsulfamic acid, E 952 is neutralized and refined with sodium hydroxide.
Synthesis of Cyclohexylamine and Sulfur Trioxide This is the production method of Baldwin-Montrose Chemical Company in the United States.
(CH3)3N SO3 →(CH3)3NSO3[C6H11NH2] →[NaOH] → C6H11NHSO3Na Dissolve trimethylamine and sulfur trioxide in tetrachloroethylene solvent respectively, and then mix and react to form a suspension of trimethylamine-sulfur trioxide complex.
This suspension is then added to an aqueous solution of cyclohexylamine and sodium hydroxide, and reacted at 60~70°C to form sodium cyclohexanesulfonate.
40g of liquid SO3 can also be dissolved in 200 mLCH2C12, added dropwise to 150mL of solution dissolved with 56g of triethylamine at-I0 ℃, and reacted at a constant temperature for 15min to generate triethylamine sulfur trioxide complex.
The equimolar cyclohexylamine was added dropwise at 20 ℃ for 1h.
After the reaction was complete, NaOH solution of 250mL 10% was added and reacted at 60 ℃ for 1h.
E 952 is obtained by concentration, cooling, crystallization, suction filtration and drying of the separated water layer, and the yield is about 95%.
In addition, Japan's Nido Chemical Company adopts the process route of gas phase reaction of sulfur trioxide and cyclohexylamine.
Cyclohexylamine and sulfamic acid (or salt) synthesis method Japan Jifu Pharmaceutical Co., Ltd. uses cyclohexylamine and sodium sulfamate as raw materials to produce cyclamate.
The reaction is carried out in a light oil solvent at 180~200 ℃.
After the reaction, it is crystallized and recrystallized to obtain the finished product, and the mother liquor is returned to the reactor for reuse.
This method is easy to obtain raw materials, simple operation, easy recovery of solvent and high yield.
Domestic research on the optimization of the process conditions reported that 25g of cyclohexylamine was added dropwise to a mixture of 10g of sulfamic acid and 35g of light oil, reacted at 165 ℃ for 3h, then cooled to below 130 ℃, 41g of 10% sodium bicarbonate solution was added to dissolve the product, then distilled to recover light oil and cyclohexylamine, and finally the crude product was recrystallized with 97.5% yield.
C6H11NH2 + NH2SO3Na → C6H11NHSO3Na + NH3 ↑ Japan Toyo Chemical Co., Ltd. uses cyclohexylamine and sulfamic acid as raw materials to produce cyclamate at 160~179 ℃ and o-dichlorobenzene. The second reaction temperature is controlled below 130 ℃.
The unreacted cyclohexylamine and o-dichlorobenzene are steamed out with steam and reused.
The reactants are crystallized and recrystallized to obtain the finished product.
The raw materials of this method are cheap and easy to obtain, the solvent is easy to recover, the reaction time is short, and the yield is high.
2CaH11NH2 + NH2SO3H → C6H11NHSO3NH3C6H11[NaOH] → Synthesis of C6H11NHSO3Na Cyclohexylamine and Chlorosulfonic Acid This is the production method of a Japanese company.
2C6H11NH2 + ClSO3H[<5 ℃ = → C6H11NHSO3NH3C6H11[NaOH] → C6H11NHSO3Na reaction After separation, concentration and extraction, 95% finished products are obtained.
The method has cheap raw materials and fast reaction, but has more side reactions and serious equipment corrosion.
Using cyclohexylamine as raw material, sulfonated with chlorosulfonic acid or sulfamate to cyclohexylsulfamic acid and then reacted with sodium hydroxide.
Reactivity Profile
E 952 is incompatible with strong oxidizing agents, strong acids and strong bases.
Also incompatible with nitrites in acid solution.
Has only limited compatibility with potassium salts .
Synonyms
SODIUM CYCLAMATE
139-05-9
Sodium N-cyclohexylsulfamate
Sodium cyclohexylsulfamate
Sucaryl sodium
Cyclamic acid sodium salt
Asugryn
Sodium cyclohexanesulfamate
Cyclamate sodium
Sulfamic acid, cyclohexyl-, monosodium salt
Cyclamate, sodium
Assugrin
Ibiosuc
Suessette
Suestamin
Sugarin
Sugaron
Sodium sucaryl
Dulzor-Etas
Hachi-Sugar
Sucrum 7
sodium;N-cyclohexylsulfamate
Cyclamate, sodium salt
Natriumzyklamate
Cyclohexylsulfamate sodium
CHEBI:82431
Cyclamate sodium/ saccharin sodium
Cyclamic acid (sodium)
1I6F42RME1
61373-78-2
N-Cyclohexylsulfamic acid sodium
Cyclohexanesulfamic acid, sodium salt
Cyclohexanesulfamic acid, monosodium salt
E952
Natrii cyclamas
Sodium cyclamate (INN)
Ciclamato sodico
Assurgrin feinsuss
Assurgrin vollsuss
Natrium cyclamicum
Cyclamate de sodium
SODIUM CYCLAMATE [INN]
Natrium cyclohexylsulfamat
Natriumzyklamate [German]
Ciclamato sodico [DCIT]
Cyclohexylsulphamate sodium
Natriumcyclohexylamidosulfat
Sodium cyclohexyl sulfamate
Sodium cyclohexanesulphamate
Natraiumcyclohexylamidosulfat
Sodium cyclohexyl sulphamate
Sodium cyclohexylsulphamidate
Monosodium cyclohexylsulfamate
CCRIS 187
Natrii cyclamas [INN-Latin]
Sodium cyclohexyl amidosulphate
NSC-42195
Cyclamate de sodium [INN-French]
N-Cyklohexylsulfamat sodny [Czech]
Cyclohexylsulfamic acid, sodium salt
EINECS 205-348-9
N-Cyklohexylsulfamat sodny
NSC 42195
sodiumcyclamate
UNII-1I6F42RME1
Cyclohexylsulphamic acid, monosodium salt
Cyclohexanesulphamic acid, monosodium salt
AI3-24213
Sulfamic acid, cylclohexyl-, monosodium salt
Sodium cyclamate [INN:BAN:NF]
Cyclamic acid sodium
N-Cyclohexylsulfamic acid sodium salt
DSSTox_CID_355
DSSTox_RID_75534
DSSTox_GSID_20355
SCHEMBL66221
Sodium N-Cyclohexanesulfamate
MLS004773942
SODIUM CYCLAMATE [II]
CHEMBL273977
SODIUM CYCLAMATE [IARC]
SODIUM CYCLAMATE [INCI]
DTXSID6020355
INS NO. 952(IV)
Sodium(sulfonatoamino)cyclohexane
INS-952(IV)
SODIUM CYCLAMATE ANHYDROUS
SODIUM CYCLAMATE [MART.]
SODIUM CYCLAMATE [USP-RS]
SODIUM CYCLAMATE [WHO-DD]
bis(1-piperidinecarbodithioato)-zin
Tox21_202781
zinc-N-pentamethylene dithiocarbamate
BDBM50500683
E-952(IV)
MFCD00003827
AKOS015897277
N-Cyclohexanesulfamic Acid Sodium Salt
CCG-213831
CS-W015555
HY-W014839
SODIUM CYCLAMATE [EP MONOGRAPH]
NCGC00164316-01
NCGC00260327-01
SODIUM (SULFONATOAMINO)CYCLOHEXANE
AS-17602
CAS-139-05-9
SMR003500667
FT-0624198
C19378
D02443
D70402
Q407786
Sulfamic acid, N-cyclohexyl-, sodium salt (1:1)
J-007216
N-Cyclohexylsulfamic acid sodium 1000 microg/mL in Acetonitrile:Water
